Authors:Liliya Tyutyunyk-Massey; Syed U. Haqqani; Reshma Mandava; Kirubel Kentiba; Mallika Dammalapati; Nga Dao; Joshua Haueis; David Gewirtz; Joseph W. Landry Pages: 1 - 39 Abstract: Publication date: 2018 Source:Advances in Cancer Research, Volume 138 Author(s): Liliya Tyutyunyk-Massey, Syed U. Haqqani, Reshma Mandava, Kirubel Kentiba, Mallika Dammalapati, Nga Dao, Joshua Haueis, David Gewirtz, Joseph W. Landry Cancer chemotherapeutic drugs have greatly advanced our ability to successfully treat a variety of human malignancies. The different forms of stress produced by these agents in cancer cells result in both cell autonomous and cell nonautonomous effects. Desirable cell autonomous effects include reduced proliferative potential, cellular senescence, and cell death. More recently recognized cell nonautonomous effects, usually in the form of stimulating an antitumor immune response, have significant roles in therapeutic efficiency for a select number of chemotherapies. Unfortunately, the success of these therapeutics is not universal as not all tumors respond to treatment, and those that do respond will frequently relapse into therapy-resistant disease. Numerous strategies have been developed to sensitize tumors toward chemotherapies as a means to either improve initial responses, or serve as a secondary treatment strategy for therapy-resistant disease. Recently, targeting epigenetic regulators has emerged as a viable method of sensitizing tumors to the effects of chemotherapies, many of which are cytotoxic. In this review, we summarize these strategies and propose a path for future progress.
Authors:Diana Fang; Eduardo N. Maldonado Pages: 41 - 69 Abstract: Publication date: 2018 Source:Advances in Cancer Research, Volume 138 Author(s): Diana Fang, Eduardo N. Maldonado Cancer metabolism is emerging as a chemotherapeutic target. Enhanced glycolysis and suppression of mitochondrial metabolism characterize the Warburg phenotype in cancer cells. The flux of respiratory substrates, ADP, and Pi into mitochondria and the release of mitochondrial ATP to the cytosol occur through voltage-dependent anion channels (VDACs) located in the mitochondrial outer membrane. Catabolism of respiratory substrates in the Krebs cycle generates NADH and FADH2 that enter the electron transport chain (ETC) to generate a proton motive force that maintains mitochondrial membrane potential (ΔΨ) and is utilized to generate ATP. The ETC is also the major cellular source of mitochondrial reactive oxygen species (ROS). αβ-Tubulin heterodimers decrease VDAC conductance in lipid bilayers. High constitutive levels of cytosolic free tubulin in intact cancer cells close VDAC decreasing mitochondrial ΔΨ and mitochondrial metabolism. The VDAC–tubulin interaction regulates VDAC opening and globally controls mitochondrial metabolism, ROS formation, and the intracellular flow of energy. Erastin, a VDAC-binding molecule lethal to some cancer cell types, and erastin-like compounds identified in a high-throughput screening antagonize the inhibitory effect of tubulin on VDAC. Reversal of tubulin inhibition of VDAC increases VDAC conductance and the flux of metabolites into and out of mitochondria. VDAC opening promotes a higher mitochondrial ΔΨ and a global increase in mitochondrial metabolism leading to high cytosolic ATP/ADP ratios that inhibit glycolysis. VDAC opening also increases ROS production causing oxidative stress that, in turn, leads to mitochondrial dysfunction, bioenergetic failure, and cell death. In summary, antagonism of the VDAC–tubulin interaction promotes cell death by a “double-hit model” characterized by reversion of the proproliferative Warburg phenotype (anti-Warburg) and promotion of oxidative stress.
Authors:Steven A. Rosenzweig Pages: 71 - 98 Abstract: Publication date: 2018 Source:Advances in Cancer Research, Volume 138 Author(s): Steven A. Rosenzweig Resistance to chemotherapeutic drugs exemplifies the greatest hindrance to effective treatment of cancer patients. The molecular mechanisms responsible have been investigated for over 50 years and have revealed the lack of a single cause, but instead, multiple mechanisms including induced expression of membrane transporters that pump drugs out of cells (multidrug resistance (MDR) phenotype), changes in the glutathione system, and altered metabolism. Treatment of cancer patients/cancer cells with chemotherapeutic agents and/or molecularly targeted drugs is accompanied by acquisition of resistance to the treatment administered. Chemotherapeutic agent resistance was initially assumed to be due to induction of mutations leading to a resistant phenotype. While this has occurred for molecularly targeted drugs, it is clear that drugs selectively targeting tyrosine kinases (TKs) cause the acquisition of mutational changes and resistance to inhibition. The first TK to be targeted, Bcr-Abl, led to the generation of several drugs including imatinib, dasatinib, and sunitinib that provided a rich understanding of this phenomenon. It became clear that mutations alone were not the only cause of resistance. Additional mechanisms were involved, including alternative splicing, alternative/compensatory signaling pathways, and epigenetic changes. This review will focus on resistance to tyrosine kinase inhibitors (TKIs), receptor TK (RTK)-directed antibodies, and antibodies that inactivate specific RTK ligands. New approaches and concepts aimed at avoiding the generation of drug resistance will be examined. Many RTKs, including the IGF-1R, are dependence receptors that induce ligand-independent apoptosis. How this signaling paradigm has implications on therapeutic strategies will also be considered.
Authors:Scott T. Eblen Pages: 99 - 142 Abstract: Publication date: 2018 Source:Advances in Cancer Research, Volume 138 Author(s): Scott T. Eblen The extracellular-regulated kinases ERK1 and ERK2 are evolutionarily conserved, ubiquitous serine–threonine kinases that are involved in regulating cellular signaling in both normal and pathological conditions. Their expression is critical for development and their hyperactivation is a major factor in cancer development and progression. Since their discovery as one of the major signaling mediators activated by mitogens and Ras mutation, we have learned much about their regulation, including their activation, binding partners and substrates. In this review I will discuss some of what has been discovered about the members of the Ras to ERK pathway, including regulation of their activation by growth factors and cell adhesion pathways. Looking downstream of ERK activation I will also highlight some of the many ERK substrates that have been discovered, including those involved in feedback regulation, cell migration and cell cycle progression through the control of transcription, pre-mRNA splicing and protein synthesis.
Authors:Mitchell E. Menezes; Praveen Bhoopathi; Anjan K. Pradhan; Luni Emdad; Swadesh K. Das; Chunqing Guo; Xiang-Yang Wang; Devanand Sarkar; Paul B. Fisher Pages: 143 - 182 Abstract: Publication date: 2018 Source:Advances in Cancer Research, Volume 138 Author(s): Mitchell E. Menezes, Praveen Bhoopathi, Anjan K. Pradhan, Luni Emdad, Swadesh K. Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B. Fisher Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24). Discovered in the early 1990s, MDA-7/IL-24 has proven to be a potent, near ubiquitous cancer suppressor gene capable of inducing cancer cell death through apoptosis and toxic autophagy in cancer cells in vitro and in preclinical animal models in vivo. In addition, MDA-7/IL-24 embodied profound anticancer activity in a Phase I/II clinical trial following direct injection with an adenovirus (Ad.mda-7; INGN-241) in tumors in patients with advanced cancers. In multiple independent studies, MDA-7/IL-24 has been implicated in many pathological states involving inflammation and may play a role in inflammatory bowel disease, psoriasis, cardiovascular disease, rheumatoid arthritis, tuberculosis, and viral infection. This review provides an up-to-date review on the multifunctional gene mda-7/IL-24, which may hold potential for the therapy of not only cancer, but also other pathological states.
Authors:Jesse J. McClure; Xiaoyang Li; C. James Chou Pages: 183 - 211 Abstract: Publication date: 2018 Source:Advances in Cancer Research, Volume 138 Author(s): Jesse J. McClure, Xiaoyang Li, C. James Chou Since the identification and cloning of human histone deacetylases (HDACs) and the rapid approval of vorinostat (Zolinza®) for the treatment of cutaneous T-cell lymphoma, the field of HDAC biology has met many initial successes. However, many challenges remain due to the complexity involved in the lysine posttranslational modifications, epigenetic transcription regulation, and nonepigenetic cellular signaling cascades. In this chapter, we will: review the discovery of the first HDAC inhibitor and present discussion regarding the future of next-generation HDAC inhibitors, give an overview of different classes of HDACs and their differences in lysine deacylation activity, discuss different classes of HDAC inhibitors and their HDAC isozyme preferences, and review HDAC inhibitors’ preclinical studies, their clinical trials, their pharmacokinetic challenges, and future direction. We will also discuss the likely reason for the failure of multiple HDAC inhibitor clinical trials in malignancies other than lymphoma and multiple myeloma. In addition, the potential molecular mechanism(s) that may play a key role in the efficacy and therapeutic response rate in the clinic and the likely patient population for HDAC therapy will be discussed.
Authors:Mitchell E. Menezes; Sarmistha Talukdar; Stephen L. Wechman; Swadesh K. Das; Luni Emdad; Devanand Sarkar; Paul B. Fisher Pages: 213 - 237 Abstract: Publication date: 2018 Source:Advances in Cancer Research, Volume 138 Author(s): Mitchell E. Menezes, Sarmistha Talukdar, Stephen L. Wechman, Swadesh K. Das, Luni Emdad, Devanand Sarkar, Paul B. Fisher The incidence of melanoma has continued to increase over the past 30 years. Hence, developing effective therapies to treat both primary and metastatic melanoma are essential. While advances in targeted therapy and immunotherapy have provided novel therapeutic options to treat melanoma, gene therapy may provide additional strategies for the treatment of metastatic melanoma clinically. This review focuses upon the challenges and opportunities that gene therapy provides for targeting melanoma. We begin with a discussion of the various gene therapy targets which are relevant to melanoma. Next, we explore the gene therapy clinical trials that have been conducted for treating melanoma. Finally, challenges faced in gene therapy as well as combination therapies for targeting melanoma, which may circumvent these obstacles, will be discussed. Targeted combination gene therapy strategies hold significant promise for developing the most effective therapeutic outcomes, while reducing the toxicity to noncancerous cells, and would integrate the patient's immune system to diminish melanoma progression. Next-generation vectors designed to embody required safety profiles and “theranostic” attributes, combined with immunotherapeutic strategies would be critical in achieving beneficial management and therapeutic outcomes in melanoma patients.
Authors:Masoud H. Manjili Pages: 17 - 36 Abstract: Publication date: 2018 Source:Advances in Cancer Research, Volume 137 Author(s): Masoud H. Manjili In the past decades, a variety of strategies have been explored to cure cancer by means of immunotherapy, which is less toxic compared with chemotherapy or radiation therapy, and could establish memory for long-lasting protection against tumor recurrence. These endeavors have been successful in offering therapeutic antibodies, vaccines, or cellular immunotherapies, which resulted in prolonging survival of some cancer patients; however, complete cures have not been consistently achieved. The conception, design, and implementation of these promising immunotherapeutic strategies have been influenced by two schools of thought in immunology, which include the “self–nonself” (SNS) model and the “danger” model. Further progress in cancer immunotherapy to achieve consistent cancer cures requires an evolution in our understanding of how the immune system works. The purpose of this review is to revisit premises and limitations of the SNS and danger models based on the outcomes of cancer immunotherapies by suggesting that both models are two sides of the same coin describing how the immune response is induced against cancer. However, neither explains how the immune response succeeds or fails in eliminating the tumor. To this end, the adaptation model has been proposed to explain efficacy of the immune response for achieving cancer cure.
Authors:Laurence Booth; Jane L. Roberts; John Kirkwood; Andrew Poklepovic; Paul Dent Abstract: Publication date: Available online 3 January 2018 Source:Advances in Cancer Research Author(s): Laurence Booth, Jane L. Roberts, John Kirkwood, Andrew Poklepovic, Paul Dent For several years, it has been known that histone deacetylase inhibitors have the potential to alter the immunogenicity of tumor cells exposed to checkpoint inhibitory immunotherapy antibodies. HDAC inhibitors can rapidly reduce expression of PD-L1 and increase expression of MHCA in various tumor types that subsequently facilitate the antitumor actions of checkpoint inhibitors. Recently, we have discovered that drug combinations which cause a rapid and intense autophagosome formation also can modulate the expression of HDAC proteins that control tumor cell immunogenicity via their regulation of PD-L1 and MHCA. These drug combinations, in particular those using the irreversible ERBB1/2/4 inhibitor neratinib, can result in parallel in the internalization of growth factor receptors as well as fellow-traveler proteins such as mutant K-RAS and mutant N-RAS into autophagosomes. The drug-induced autophagosomes contain HDAC proteins/signaling proteins whose expression is subsequently reduced by lysosomal degradation processes. These findings argue that cancer therapies which strongly promote autophagosome formation and autophagic flux may facilitate the subsequent use of additional antitumor modalities using checkpoint inhibitor antibodies.
Authors:Stephen L Wechman; Anjan K Pradhan; Rob DeSalle; Swadesh K. Das; Luni Emdad; Devanand Sarkar; Paul B. Fisher Abstract: Publication date: Available online 27 December 2017 Source:Advances in Cancer Research Author(s): Stephen L Wechman, Anjan K Pradhan, Rob DeSalle, Swadesh K. Das, Luni Emdad, Devanand Sarkar, Paul B. Fisher Autophagy is a functionally conserved self-degradation process that facilitates the survival of eukaryotic life via the management of cellular bioenergetics and maintenance of the fidelity of genomic DNA. The first known autophagy inducer was Beclin-1. Beclin-1 is expressed in multicellular eukaryotes ranging throughout plants to animals, comprising a nonmonophyllic group, as shown in this report via aggressive BLAST searches. In humans, Beclin-1 is a haploinsuffient tumor suppressor as biallelic deletions have not been observed in patient tumors clinically. Therefore, Beclin-1 fails the Knudson hypothesis, implicating expression of at least one Beclin-1 allele is essential for cancer cell survival. However, Beclin-1 is frequently monoallelically deleted in advanced human cancers and the expression of two Beclin-1 allelles is associated with greater anticancer effects. Overall, experimental evidence suggests that Beclin-1 inhibits tumor formation, angiogenesis, and metastasis alone and in cooperation with the tumor suppressive molecules UVRAG, Bif-1, Ambra1, and MDA-7/IL-24 via diverse mechanisms of action. Conversely, Beclin-1 is upregulated in cancer stem cells (CSCs), portending a role in cancer recurrence, and highlighting this molecule as an intriguing molecular target for the treatment of CSCs. Many aspects of Beclin-1’s biological effects remain to be studied. The consequences of these BLAST searches on the molecular evolution of Beclin-1, and the eukaryotic branches of the tree of life, are discussed here in greater detail with future inquiry focused upon protist taxa. Also in this review, the effects of Beclin-1 on tumor suppression and cancer malignancy are discussed. Beclin-1 holds significant promise for the development of novel targeted cancer therapeutics and is anticipated to lead to a many advances in our understanding of eukaryotic evolution, multicellularity, and even the treatment of CSCs in the coming decades.
Authors:Sarah P. Short; Christopher S. Williams Pages: 49 - 83 Abstract: Publication date: 2017 Source:Advances in Cancer Research, Volume 136 Author(s): Sarah P. Short, Christopher S. Williams Selenium is a micronutrient essential to human health and has long been associated with cancer prevention. Functionally, these effects are thought to be mediated by a class of selenium-containing proteins known as selenoproteins. Indeed, many selenoproteins have antioxidant activity which can attenuate cancer development by minimizing oxidative insult and resultant DNA damage. However, oxidative stress is increasingly being recognized for its “double-edged sword” effect in tumorigenesis, whereby it can mediate both negative and positive effects on tumor growth depending on the cellular context. In addition to their roles in redox homeostasis, recent work has also implicated selenoproteins in key oncogenic and tumor-suppressive pathways. Together, these data suggest that the overall contribution of selenoproteins to tumorigenesis is complicated and may be affected by a variety of factors. In this review, we discuss what is currently known about selenoproteins in tumorigenesis with a focus on their contextual roles in cancer development, growth, and progression.
Authors:Monica A. Valentovic Abstract: Publication date: Available online 15 December 2017 Source:Advances in Cancer Research Author(s): Monica A. Valentovic Cancer is one of the top three causes of death in the United States. The treatment regimen for controlling cancer includes a number of approaches depending on the classification of the tumor. Treatment may include radiation, surgery, and cancer chemotherapy agents as well as other interventions. Natural products have been identified for centuries to contain active pharmacologic activity and have been a starting point for numerous drugs which are currently on the market. Resveratrol (RES) is a natural product generated in plants in response to environmental stress and growing conditions. RES has been recognized since 1997 to possess anticancer activity. This review discusses the dietary sources of RES and the relative amounts present in the various food sources. A few limited clinical studies have explored RES effects in patients with prostate and colorectal cancer and have suggested some beneficial results. Future studies need to expand the sample size for clinical examination of RES in order to provide a better profile for the potential benefit of RES in cancer patients. This review also describes the potential mechanisms of RES as an antioxidant and in alteration of cell signaling. Another aspect for the role of RES in cancer may be in the interaction with cancer chemotherapy agents. Cisplatin is a cancer chemotherapy agent used for the treatment of bladder, testicular, ovarian, and many other cancers. Cisplatin usage is associated with a high risk of nephrotoxicity. Experimental studies suggest that RES may reduce cisplatin renal toxicity. The proposed mechanisms of protection are reviewed.
Authors:Narsireddy Amreddy; Anish Babu; Ranganayaki Muralidharan; Janani Panneerselvam; Akhil Srivastava; Rebaz Ahmed; Meghna Mehta; Anupama Munshi; Rajagopal Ramesh Abstract: Publication date: Available online 7 December 2017 Source:Advances in Cancer Research Author(s): Narsireddy Amreddy, Anish Babu, Ranganayaki Muralidharan, Janani Panneerselvam, Akhil Srivastava, Rebaz Ahmed, Meghna Mehta, Anupama Munshi, Rajagopal Ramesh Effective and safe delivery of anticancer agents is among the major challenges in cancer therapy. The majority of anticancer agents are toxic to normal cells, have poor bioavailability, and lack in vivo stability. Recent advancements in nanotechnology provide safe and efficient drug delivery systems for successful delivery of anticancer agents via nanoparticles. The physicochemical and functional properties of the nanoparticle vary for each of these anticancer agents, including chemotherapeutics, nucleic acid-based therapeutics, small molecule inhibitors, and photodynamic agents. The characteristics of the anticancer agents influence the design and development of nanoparticle carriers. This review focuses on strategies of nanoparticle-based drug delivery for various anticancer agents. Recent advancements in the field are also highlighted, with suitable examples from our own research efforts and from the literature.
Authors:Santanu Maji; Sanjay Panda; Sabindra K. Samal; Omprakash Shriwas; Rachna Rath; Maurizio Pellecchia; Luni Emdad; Swadesh K. Das; Paul B. Fisher; Rupesh Dash Abstract: Publication date: Available online 6 December 2017 Source:Advances in Cancer Research Author(s): Santanu Maji, Sanjay Panda, Sabindra K. Samal, Omprakash Shriwas, Rachna Rath, Maurizio Pellecchia, Luni Emdad, Swadesh K. Das, Paul B. Fisher, Rupesh Dash Cancer is a daunting global problem confronting the world's population. The most frequent therapeutic approaches include surgery, chemotherapy, radiotherapy, and more recently immunotherapy. In the case of chemotherapy, patients ultimately develop resistance to both single and multiple chemotherapeutic agents, which can culminate in metastatic disease which is a major cause of patient death from solid tumors. Chemoresistance, a primary cause of treatment failure, is attributed to multiple factors including decreased drug accumulation, reduced drug–target interactions, increased populations of cancer stem cells, enhanced autophagy activity, and reduced apoptosis in cancer cells. Reprogramming tumor cells to undergo drug-induced apoptosis provides a promising and powerful strategy for treating resistant and recurrent neoplastic diseases. This can be achieved by downregulating dysregulated antiapoptotic factors or activation of proapoptotic factors in tumor cells. A major target of dysregulation in cancer cells that can occur during chemoresistance involves altered expression of Bcl-2 family members. Bcl-2 antiapoptotic molecules (Bcl-2, Bcl-xL, and Mcl-1) are frequently upregulated in acquired chemoresistant cancer cells, which block drug-induced apoptosis. We presently overview the potential role of Bcl-2 antiapoptotic proteins in the development of cancer chemoresistance and overview the clinical approaches that use Bcl-2 inhibitors to restore cell death in chemoresistant and recurrent tumors.
Authors:Giuseppe Murdolo; Desirée Bartolini; Cristina Tortoioli; Marta Piroddi; Pierangelo Torquato; Francesco Galli Abstract: Publication date: Available online 12 October 2017 Source:Advances in Cancer Research Author(s): Giuseppe Murdolo, Desirée Bartolini, Cristina Tortoioli, Marta Piroddi, Pierangelo Torquato, Francesco Galli Selenium (Se) is an essential micronutrient that functions as “redox gatekeeper” and homeostasis factor of normal and cancer cells. Epidemiology and experimental studies, in the last years suggested that both inorganic and organic forms of Se may have favorable health effects. In this regard, a protective action of Se on cellular systems that may help preventing cancer cell differentiation has been demonstrated, while the hypothesis that Se compounds may cure cancer and its metastatic diffusion appears speculative and is still a matter of investigation. Indeed, the overall actions of Se compounds in carcinogenesis are controversial. The recognition that cancer is a stem cell disease instigated major paradigm shifts in our basic understanding of cancer and attracted a great deal of interest. Although current treatment approaches in cancer are grounded in the need to kill the majority of cancer cells, targeting cancer stem cells (CSCs) may hold great potential in improving cancer treatment. In this respect, Se compounds have been demonstrated modulating numerous signaling pathways involved in CSC biology and these findings are now stimulating further research on optimal Se concentrations, most effective and cancer-specific Se compounds, and inherent pathways involved in redox and metabolic regulation of CSCs. In this review, we summarize the current knowledge about the effects of Se compounds on CSCs, by focusing on redox-dependent pathways and main gene regulation checkpoints that affect self-renewal, differentiation, and migration responses in this subpopulation of cancer cells.
Authors:Desirée Bartolini; Luca Sancineto; Andreza Fabro de Bem; Kenneth D. Tew; Claudio Santi; Rafael Radi; Pierangelo Toquato; Francesco Galli Abstract: Publication date: Available online 28 September 2017 Source:Advances in Cancer Research Author(s): Desirée Bartolini, Luca Sancineto, Andreza Fabro de Bem, Kenneth D. Tew, Claudio Santi, Rafael Radi, Pierangelo Toquato, Francesco Galli In vitro and in vivo experimental models clearly demonstrate the efficacy of Se compounds as anticancer agents, contingent upon chemical structures and concentrations of test molecules, as well as on the experimental model under investigation that together influence cellular availability of compounds, their molecular dynamics and mechanism of action. The latter includes direct and indirect redox effects on cellular targets by the activation and altered compartmentalization of molecular oxygen, and the interaction with protein thiols and Se proteins. As such, Se compounds interfere with the redox homeostasis and signaling of cancer cells to produce anticancer effects that include alterations in key regulatory elements of energy metabolism and cell cycle checkpoints that ultimately influence differentiation, proliferation, senescence, and death pathways. Cys-containing proteins and Se proteins involved in the response to Se compounds as sensors and transducers of anticancer signals, i.e., the pharmacoproteome of Se compounds, are described and include critical elements in the different phases of cancer onset and progression from initiation and escape of immune surveillance to tumor growth, angiogenesis, and metastasis. The efficacy and mode of action on these compounds vary depending on the inorganic and organic form of Se used as either supplement or pharmacological agent. In this regard, differences in experimental/clinical protocols provide options for either chemoprevention or therapy in different human cancers.
Authors:Camile C. Fontelles; Thomas P. Ong Abstract: Publication date: Available online 21 September 2017 Source:Advances in Cancer Research Author(s): Camile C. Fontelles, Thomas P. Ong Selenium (Se) is a micronutrient with promising breast cancer prevention and treatment potential. There is extensive preclinical evidence of Se mammary carcinogenesis inhibition. Evidence from epidemiological studies is, however, unclear and intervention studies are rare. Here, we examine Se chemoprotection, chemoprevention, and chemotherapy effects in breast cancer, focusing on associated cellular and molecular mechanisms. Se exerts its protective actions through multiple mechanisms that involve antioxidant activities, induction of apoptosis, and inhibition of DNA damage, cell proliferation, angiogenesis, and invasion. New aspects of Se actions in breast cancer have emerged such as the impact of genetic polymorphisms on Se metabolism and response, new functions of selenoproteins, epigenetic modulation of gene expression, and long-term influence of early-life exposure on disease risk. Opportunity exists to design interventional studies with Se for breast cancer prevention and treatment taking into consideration these key aspects.
Authors:Jablonska Ewa; Reszka Edyta Abstract: Publication date: Available online 12 September 2017 Source:Advances in Cancer Research Author(s): Jablonska Ewa, Reszka Edyta Chemopreventive activity of selenium (Se) may influence epigenome. In this review, we have discussed two aspects of Se and epigenetics in cancer, related to (1) the association between Se and epigenetic regulation in cancer development and prevention; (2) epigenetic modification of selenoprotein-encoding genes in different cancers. In both issues, we focused on DNA methylation as the most investigated epigenetic mechanism. The existing evidence from experimental data in human cancer cell lines, rodents, and human studies in cancer-free subjects indicates that: high Se exposure leads to the inhibition of DNA methyltransferase expression/activity; the association between Se and global methylation remains unclear and requires further investigation with respect to the underlying mechanisms and possible nonlinear character of this relationship; Se affects methylation of specific tumor suppressor genes, possibly in a sex-dependent manner; and cancer phenotype is often characterized by altered methylation of selenoprotein-encoding genes, mainly glutathione peroxidase 3.
Authors:Michael P. Marciel; Peter R. Hoffmann Abstract: Publication date: Available online 1 September 2017 Source:Advances in Cancer Research Author(s): Michael P. Marciel, Peter R. Hoffmann Cancer survival is largely impacted by the dissemination of cancer cells from the original tumor site to secondary tissues or organs through metastasis. Targets for antimetastatic therapies have recently become a focus of research, but progress will require a better understanding of the molecular mechanisms driving metastasis. Selenoproteins play important roles in many of the cellular activities underlying metastasis including cell adhesion, matrix degradation and migration, invasion into the blood and extravasation into secondary tissues, and subsequent proliferation into metastatic tumors along with the angiogenesis required for growth. In this review the roles identified for different selenoproteins in these steps and how they may promote or inhibit metastatic cancers is discussed. These roles include selenoenzyme modulation of redox tone and detoxification of reactive oxygen species, calcium homeostasis and unfolded protein responses regulated by endoplasmic reticulum selenoproteins, and the multiple physiological responses influenced by other selenoproteins.
Authors:Bastihalli T. Diwakar; Arvind M. Korwar; Robert F. Paulson; K. Sandeep Prabhu Abstract: Publication date: Available online 31 August 2017 Source:Advances in Cancer Research Author(s): Bastihalli T. Diwakar, Arvind M. Korwar, Robert F. Paulson, K. Sandeep Prabhu Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited replicative potential, but evade chemotherapy drugs through cellular quiescence. CSCs are able to give rise to bulk tumor cells that have the capability to override antiproliferative signals and evade apoptosis. Numerous pathways are dysregulated in tumor cells, where increased levels of prooxidant reactive oxygen and nitrogen species can lead to localized inflammation to exacerbate all three stages of tumorigenesis: initiation, progression, and metastasis. Modulation of cellular metabolism in tumor cells as well as immune cells in the tumor microenvironment (TME) can impact inflammatory networks. Altering these pathways can potentially serve as a portal for therapy. It is well known that selenium, through selenoproteins, modulates inflammatory pathways in addition to regulating redox homeostasis in cells. Therefore, selenium has the potential to impact the interaction between tumor cells, CSCs, and immune cells. In the sections later, we review the current status of knowledge regarding this interaction, with reference to leukemia stem cells, and the importance of selenium-dependent regulation of inflammation as a potential mechanism to affect the TME and tumor cell survival.
Authors:Anna P. Kipp Abstract: Publication date: Available online 23 August 2017 Source:Advances in Cancer Research Author(s): Anna P. Kipp Five out of eight human glutathione peroxidases (GPxes) are selenoproteins and thus their expression depends on the selenium (Se) supply. Most Se-dependent GPxes are downregulated in tumor cells, while only GPx2 is considerably upregulated. Whether expression profiles of GPxes predict tumor development and patient survival is controversially discussed. Also, results from in vitro and in vivo studies modulating the expression of GPx isoforms provide evidence for both anti- and procarcinogenic mechanisms. GPxes are able to reduce hydroperoxides, which otherwise would damage DNA, possibly resulting in DNA mutations, modulate redox-sensitive signaling pathways affecting proliferation, differentiation, and cellular metabolism or initiate cell death. Considering these different processes, the role and functions of individual Se-dependent GPx isoforms will be discussed herein in the context of tumorigenesis.
Authors:Elias S.J. Arnér Abstract: Publication date: Available online 23 August 2017 Source:Advances in Cancer Research Author(s): Elias S.J. Arnér The cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, encoded in human by TXNRD1) is implied to have several different roles in relation to cancer. Its physiologic functions may protect normal cells from carcinogenesis, but may also promote cancer progression if carcinogenesis nonetheless occurs. With distinct links to Nrf2 signaling, ribonucleotide reductase-dependent production of deoxyribonucleotides and its support of several antioxidant systems counteracting oxidative stress, the metabolic pathways regulated, and affected by TrxR1, are altogether of crucial importance in cancer. These pathways and causal relationships are at the same time highly intricate. In spite of the complexity in the cellular redox networks, several observations discussed in this chapter suggest that specific targeting of TrxR1 may be promising as a mechanistic principle for anticancer therapy.
Authors:Katrien Van Roosbroeck; George A. Calin Abstract: Publication date: Available online 12 August 2017 Source:Advances in Cancer Research Author(s): Katrien Van Roosbroeck, George A. Calin Human cancers are characterized by a number of hallmarks, including sustained proliferative signaling, evasion of growth suppressors, activated invasion and metastasis, replicative immortality, angiogenesis, resistance to cell death, and evasion of immune destruction. As microRNAs (miRNAs) are deregulated in virtually all human cancers, they show involvement in each of the cancer hallmarks as well. In this chapter, we describe the involvement of miRNAs in cancer from a cancer hallmarks and targeted therapeutics point of view. As no miRNA-based cancer therapeutics are available to date, and the only clinical trial on miRNA-based cancer therapeutics (MRX34) was terminated prematurely due to serious adverse events, we are focusing on protein-coding miRNA targets for which targeted therapeutics in oncology are already approved by the FDA. For each of the cancer hallmarks, we selected major protein-coding players and describe the miRNAs that target them.
Authors:Alessandra Drusco; Carlo M. Croce Abstract: Publication date: Available online 12 August 2017 Source:Advances in Cancer Research Author(s): Alessandra Drusco, Carlo M. Croce More than six decades ago Watson and Crick published the chemical structure of DNA. This discovery revolutionized our approach to medical science and opened new perspectives for the diagnosis and treatment of many diseases including cancer. Since then, progress in molecular biology, together with the rapid advance of technologies, allowed to clone hundreds of protein-coding genes that were found mutated in all types of cancer. Normal and aberrant gene functions, interactions, and mechanisms of mutations were studied to identify the intricate network of pathways leading to cancer. With the acknowledgment of the genetic nature of cancer, new diagnostic, prognostic, and therapeutic strategies have been attempted and developed, but very few have found their way in the clinical field. In an effort to identify new translational targets, another great discovery has changed our way to look at genes and their functions. MicroRNAs have been the first noncoding genes involved in cancer. This review is a brief chronological history of microRNAs and cancer. Through the work of few of the greatest scientists of our times, this chapter describes the discovery of microRNAs from C. elegans to their debut in cancer and in the medical field, the concurrent development of technologies, and their future translational applications. The purpose was to share the exciting path that lead to one of the most important discoveries in cancer genetics in the past 20 years.
Authors:Marco Vinceti; Tommaso Filippini; Silvia Cilloni; Catherine M. Crespi Abstract: Publication date: Available online 12 August 2017 Source:Advances in Cancer Research Author(s): Marco Vinceti, Tommaso Filippini, Silvia Cilloni, Catherine M. Crespi The relation between selenium and cancer has been one of the most hotly debated topics in human health over the last decades. Early observational studies reported an inverse relation between selenium exposure and cancer risk. Subsequently, randomized controlled trials showed that selenium supplementation does not reduce the risk of cancer and may even increase it for some types, including advanced prostate cancer and skin cancer. An increased risk of diabetes has also been reported. These findings have been consistent in the most methodologically sound trials, suggesting that the early observational studies were misleading. Other studies have investigated selenium compounds as adjuvant therapy for cancer. Though there is currently insufficient evidence regarding the utility and safety of selenium compounds for such treatments, this issue is worthy of further investigation. The study of selenium and cancer is complicated by the existence of a diverse array of organic and inorganic selenium compounds, each with distinct biological properties, and this must be taken into consideration in the interpretation of both observational and experimental human studies.
Authors:Veronica Balatti; Yuri Pekarsky; Carlo M. Croce Abstract: Publication date: Available online 10 August 2017 Source:Advances in Cancer Research Author(s): Veronica Balatti, Yuri Pekarsky, Carlo M. Croce Noncoding RNAs are untranslated RNA molecules that can be divided into two main types: infrastructural, including transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), and regulatory, including long ncRNAs (lncRNAs) and small ncRNAs (sRNA). Among small ncRNA, the role of microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) in cancer is well documented. Recently, other small ncRNAs have been described. In particular, tRNA-derived small RNAs (tsRNA) have been found to be frequently dysregulated in cancer. Since tsRNAs can be considered unique sequences and are able to bind both Argonaute proteins (like miRNAs) and Piwi proteins (like piRNAs), their dysregulation could play a critical role in cancer by interfering with gene expression regulation at different levels. Like microRNAs, ts-53 (previously known as miR-3676) interacts with the 3′UTR of TCL1, therefore supporting a role for tsRNAs on the posttranscriptional regulation of gene expression. Like piRNAs, tsRNAs are produced as single-stranded molecules and can interact with DNA and histone methylation machinery, suggesting a role in the pretranscriptional regulation of gene expression. Herein, we describe the most recent findings about the role of tsRNAs in cancer.
Authors:Arpita S. Pal; Andrea L. Kasinski Abstract: Publication date: Available online 8 August 2017 Source:Advances in Cancer Research Author(s): Arpita S. Pal, Andrea L. Kasinski The discovery of the microRNAs, lin-4 and let-7 as critical mediators of normal development in Caenorhabditis elegans and their conservation throughout evolution has spearheaded research toward identifying novel roles of microRNAs in other cellular processes. To accurately elucidate these fundamental functions, especially in the context of an intact organism, various microRNA transgenic models have been generated and evaluated. Transgenic C. elegans (worms), Drosophila melanogaster (flies), Danio rerio (zebrafish), and Mus musculus (mouse) have contributed immensely toward uncovering the roles of multiple microRNAs in cellular processes such as proliferation, differentiation, and apoptosis, pathways that are severely altered in human diseases such as cancer. The simple model organisms, C. elegans, D. melanogaster, and D. rerio, do not develop cancers but have proved to be convenient systesm in microRNA research, especially in characterizing the microRNA biogenesis machinery which is often dysregulated during human tumorigenesis. The microRNA-dependent events delineated via these simple in vivo systems have been further verified in vitro, and in more complex models of cancers, such as M. musculus. The focus of this review is to provide an overview of the important contributions made in the microRNA field using model organisms. The simple model systems provided the basis for the importance of microRNAs in normal cellular physiology, while the more complex animal systems provided evidence for the role of microRNAs dysregulation in cancers. Highlights include an overview of the various strategies used to generate transgenic organisms and a review of the use of transgenic mice for evaluating preclinical efficacy of microRNA-based cancer therapeutics.
Authors:Anjan K. Pradhan; Luni Emdad; Swadesh K. Das; Devanand Sarkar; Paul B. Fisher Abstract: Publication date: Available online 7 August 2017 Source:Advances in Cancer Research Author(s): Anjan K. Pradhan, Luni Emdad, Swadesh K. Das, Devanand Sarkar, Paul B. Fisher MicroRNAs (miRNAs or miRs) are small 19–22 nucleotide long, noncoding, single-stranded, and multifunctional RNAs that regulate a diverse assortment of gene and protein functions that impact on a vast network of pathways. Lin-4, a noncoding transcript discovered in 1993 and named miRNA, initiated the exploration of research into these intriguing molecules identified in almost all organisms. miRNAs interfere with translation or posttranscriptional regulation of their target gene and regulate multiple biological actions exerted by these target genes. In cancer, they function as both oncogenes and tumor suppressor genes displaying differential activity in various cellular contexts. Although the role of miRNAs on target gene functions has been extensively investigated, less is currently known about the upstream regulatory molecules that regulate miRNAs. This chapter focuses on the factors and processes involved in miRNA regulation.
Authors:Catia Moutinho; Manel Esteller Abstract: Publication date: Available online 4 August 2017 Source:Advances in Cancer Research Author(s): Catia Moutinho, Manel Esteller MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression mainly at the posttranscriptional level. Similar to protein-coding genes, their expression is also controlled by genetic and epigenetic mechanisms. Disruption of these control processes leads to abnormal expression of miRNAs in cancer. In this chapter, we discuss the supportive links between miRNAs and epigenetics in the context of carcinogenesis. miRNAs can be epigenetically regulated by DNA methylation and/or specific histone modifications. However, they can themselves (epi-miRNAs) repress key enzymes that drive epigenetic remodeling and also bind to complementary sequences in gene promoters, recruiting specific protein complexes that modulate chromatin structure and gene expression. All these issues affect the transcriptional landscape of cells. Most important, in the cancer clinical scenario, knowledge about miRNAs epigenetic dysregulation can not only be beneficial as a prognostic biomarker, but can also help in the design of new therapeutic approaches.
Authors:Ryan Abstract: Publication date: Available online 4 August 2017 Source:Advances in Cancer Research Author(s): Bríd M. Ryan microRNAs (miRNAs) are a small RNA species without protein-coding potential. However, they are key modulators of protein translation. Many studies have linked miRNAs with cancer initiation, progression, diagnosis, and prognosis, and recent studies have also linked them with cancer etiology and susceptibility, especially through single-nucleotide polymorphisms (SNPs). This review discusses some of the recent advances in miRNA-SNP literature—including SNPs in miRNA genes, miRNA target sites, and the processing machinery. In addition, we highlight some emerging areas of interest, including isomiRs and non-3′UTR focused miRNA-binding mechanisms that could provide further novel insight into the relationship between miR-SNPs and cancer. Finally, we note that additional epidemiological and experimental research is needed to close the gap in our understanding of the genotype–phenotype relationship between miRNA-SNPs and cancer.
Authors:R. Casadonte; R. Longuespée; J. Kriegsmann; M. Kriegsmann Abstract: Publication date: Available online 12 January 2017 Source:Advances in Cancer Research Author(s): R. Casadonte, R. Longuespée, J. Kriegsmann, M. Kriegsmann Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technology creates a link between the molecular assessment of numerous molecules and the morphological information about their special distribution. The application of MALDI IMS on formalin-fixed paraffin-embedded (FFPE) tissue microarrays (TMAs) is suitable for large-scale discovery analyses. Data acquired from FFPE TMA cancer samples in current research are very promising, and applications for routine diagnostics are under development. With the current rapid advances in both technology and applications, MALDI IMS technology is expected to enter into routine diagnostics soon. This chapter is intended to be comprehensive with respect to all aspects and considerations for the application of MALDI IMS on FFPE cancer TMAs with in-depth notes on technical aspects.
Authors:R.J.A. Goodwin; J. Bunch; D.F. McGinnity Abstract: Publication date: Available online 10 January 2017 Source:Advances in Cancer Research Author(s): R.J.A. Goodwin, J. Bunch, D.F. McGinnity Over the last decade mass spectrometry imaging (MSI) has been integrated in to many areas of drug discovery and development. It can have significant impact in oncology drug discovery as it allows efficacy and safety of compounds to be assessed against the backdrop of the complex tumour microenvironment. We will discuss the roles of MSI in investigating compound and metabolite biodistribution and defining pharmacokinetic -pharmacodynamic relationships, analysis that is applicable to all drug discovery projects. We will then look more specifically at how MSI can be used to understand tumour metabolism and other applications specific to oncology research. This will all be described alongside the challenges of applying MSI to industry research with increased use of metrology for MSI.
Authors:G. Arentz; P. Mittal; C. Zhang; Y.-Y. Ho; M. Briggs; L. Winderbaum; M.K. Hoffmann; P. Hoffmann Abstract: Publication date: Available online 9 January 2017 Source:Advances in Cancer Research Author(s): G. Arentz, P. Mittal, C. Zhang, Y.-Y. Ho, M. Briggs, L. Winderbaum, M.K. Hoffmann, P. Hoffmann Pathologists play an essential role in the diagnosis and prognosis of benign and cancerous tumors. Clinicians provide tissue samples, for example, from a biopsy, which are then processed and thin sections are placed onto glass slides, followed by staining of the tissue with visible dyes. Upon processing and microscopic examination, a pathology report is provided, which relies on the pathologist's interpretation of the phenotypical presentation of the tissue. Targeted analysis of single proteins provide further insight and together with clinical data these results influence clinical decision making. Recent developments in mass spectrometry facilitate the collection of molecular information about such tissue specimens. These relatively new techniques generate label-free mass spectra across tissue sections providing nonbiased, nontargeted molecular information. At each pixel with spatial coordinates (x/y) a mass spectrum is acquired. The acquired mass spectrums can be visualized as intensity maps displaying the distribution of single m/z values of interest. Based on the sample preparation, proteins, peptides, lipids, small molecules, or glycans can be analyzed. The generated intensity maps/images allow new insights into tumor tissues. The technique has the ability to detect and characterize tumor cells and their environment in a spatial context and combined with histological staining, can be used to aid pathologists and clinicians in the diagnosis and management of cancer. Moreover, such data may help classify patients to aid therapy decisions and predict outcomes. The novel complementary mass spectrometry-based methods described in this chapter will contribute to the transformation of pathology services around the world.
Authors:M. Dufresne; N.H. Patterson; N. Lauzon; P. Chaurand Abstract: Publication date: Available online 27 December 2016 Source:Advances in Cancer Research Author(s): M. Dufresne, N.H. Patterson, N. Lauzon, P. Chaurand In the last decade, imaging mass spectrometry (IMS) has been the primary tool for biomolecular imaging. While it is possible to map a wide range of biomolecules using matrix-assisted laser desorption/ionization IMS ranging from high-molecular-weight proteins to small metabolites, more often than not only the most abundant easily ionisable species are detected. To better understand complex diseases such as cancer more specific and sensitive methods need to be developed to enable the detection of lower abundance molecules but also molecules that have yet to be imaged by IMS. In recent years, a big shift has occurred in the imaging community from developing wide reaching methods to developing targeted ones which increases sensitivity through the use of more specific sample preparations. This has been primarily marked by the advent of solvent-free matrix deposition methods for polar lipids, chemical derivatization for hormones and metabolites, and the use of alternative ionization agents for neutral lipids. In this chapter, we discuss two of the latest sample preparations which exploit the use of alternative ionization agents to enable the detection of certain classes of neutral lipids along with free fatty acids by high-sensitivity IMS as demonstrated within our lab.
Authors:K. Schwamborn Abstract: Publication date: Available online 21 December 2016 Source:Advances in Cancer Research Author(s): K. Schwamborn Mass spectrometry imaging (MSI) has become a valuable tool in cancer research. Even more, due to its capability to directly link molecular changes with histology, it holds the prospect to revolutionize tissue-based diagnostics. In order to learn to walk before running, however, information obtained through classical histology should not be neglected but rather used to its full capacity and integrated with mass spectrometry data to lead to a superior molecular histology synthesis. In order to achieve this, pathomorphological analyses have to be integrated into MSI analyses right from the beginning to avoid errors and pitfalls of MSI application possibly leading to incorrect or imprecise study outcomes. Such errors can be caused by different sample or tissue inherent factors or through factors in sample preparation. Future studies should, therefore, aim for a comprehensive incorporation of histology and pathology characteristics to ensure the generation of high-quality data in MSI to exploit its full capacity in tissue-based basic and translational research.
Authors:K. Schwamborn Abstract: Publication date: Available online 21 December 2016 Source:Advances in Cancer Research Author(s): K. Schwamborn Mass spectrometry imaging (MSI) has become a valuable tool in cancer research. Even more, due to its capability to directly link molecular changes with histology, it holds the prospect to revolutionize tissue-based diagnostics. In order to learn to walk before running, however, information obtained through classical histology should not be neglected but rather used to its full capacity and integrated with mass spectrometry data to lead to a superior molecular histology synthesis. In order to achieve this, pathomorphological analyses have to be integrated into MSI analyses right from the beginning to avoid errors and pitfalls of MSI application possibly leading to incorrect or imprecise study outcomes. Such errors can be caused by different sample or tissue inherent factors or through factors in sample preparation. Future studies should, therefore, aim for a comprehensive incorporation of histology and pathology characteristics to ensure the generation of high-quality data in MSI to exploit its full capacity in tissue-based basic and translational research.
Authors:R.R. Drake; T.W. Powers; E.E. Jones; E. Bruner; A.S. Mehta; P.M. Angel Abstract: Publication date: Available online 20 December 2016 Source:Advances in Cancer Research Author(s): R.R. Drake, T.W. Powers, E.E. Jones, E. Bruner, A.S. Mehta, P.M. Angel Glycosylated proteins account for a majority of the posttranslation modifications of cell surface, secreted, and circulating proteins. Within the tumor microenvironment, the presence of immune cells, extracellular matrix proteins, cell surface receptors, and interactions between stroma and tumor cells are all processes mediated by glycan binding and recognition reactions. Changes in glycosylation during tumorigenesis are well documented to occur and affect all of these associated adhesion and regulatory functions. A MALDI imaging mass spectrometry (MALDI-IMS) workflow for profiling N-linked glycan distributions in fresh/frozen tissues and formalin-fixed paraffin-embedded tissues has recently been developed. The key to the approach is the application of a molecular coating of peptide-N-glycosidase to tissues, an enzyme that cleaves asparagine-linked glycans from their protein carrier. The released N-linked glycans can then be analyzed by MALDI-IMS directly on tissue. Generally 40 or more individual glycan structures are routinely detected, and when combined with histopathology localizations, tumor-specific glycans are readily grouped relative to nontumor regions and other structural features. This technique is a recent development and new approach in glycobiology and mass spectrometry imaging research methodology; thus, potential uses such as tumor-specific glycan biomarker panels and other applications are discussed.
Authors:R.R. Drake; T.W. Powers; E.E. Jones; E. Bruner; A.S. Mehta; P.M. Angel Abstract: Publication date: Available online 20 December 2016 Source:Advances in Cancer Research Author(s): R.R. Drake, T.W. Powers, E.E. Jones, E. Bruner, A.S. Mehta, P.M. Angel Glycosylated proteins account for a majority of the posttranslation modifications of cell surface, secreted, and circulating proteins. Within the tumor microenvironment, the presence of immune cells, extracellular matrix proteins, cell surface receptors, and interactions between stroma and tumor cells are all processes mediated by glycan binding and recognition reactions. Changes in glycosylation during tumorigenesis are well documented to occur and affect all of these associated adhesion and regulatory functions. A MALDI imaging mass spectrometry (MALDI-IMS) workflow for profiling N-linked glycan distributions in fresh/frozen tissues and formalin-fixed paraffin-embedded tissues has recently been developed. The key to the approach is the application of a molecular coating of peptide-N-glycosidase to tissues, an enzyme that cleaves asparagine-linked glycans from their protein carrier. The released N-linked glycans can then be analyzed by MALDI-IMS directly on tissue. Generally 40 or more individual glycan structures are routinely detected, and when combined with histopathology localizations, tumor-specific glycans are readily grouped relative to nontumor regions and other structural features. This technique is a recent development and new approach in glycobiology and mass spectrometry imaging research methodology; thus, potential uses such as tumor-specific glycan biomarker panels and other applications are discussed.
Authors:A. Buck; M. Aichler; K. Huber; A. Walch Abstract: Publication date: Available online 20 December 2016 Source:Advances in Cancer Research Author(s): A. Buck, M. Aichler, K. Huber, A. Walch Metabolomics is a rapidly evolving and a promising research field with the expectation to improve diagnosis, therapeutic treatment prediction, and prognosis of particular diseases. Among all techniques used to assess the metabolome in biological systems, mass spectrometry imaging is the method of choice to qualitatively and quantitatively analyze metabolite distribution in tissues with a high spatial resolution, thus providing molecular data in relation to cancer histopathology. The technique is ideally suited to study tissues molecular content and is able to provide molecular biomarkers or specific mass signatures which can be used in classification or the prognostic evaluation of tumors. Recently, it was shown that FFPE tissue samples are also suitable for metabolic analyses. This progress in methodology allows access to a highly valuable resource of tissues believed to widen and strengthen metabolic discovery-driven studies.
Authors:A. Buck; M. Aichler; K. Huber; A. Walch Abstract: Publication date: Available online 20 December 2016 Source:Advances in Cancer Research Author(s): A. Buck, M. Aichler, K. Huber, A. Walch Metabolomics is a rapidly evolving and a promising research field with the expectation to improve diagnosis, therapeutic treatment prediction, and prognosis of particular diseases. Among all techniques used to assess the metabolome in biological systems, mass spectrometry imaging is the method of choice to qualitatively and quantitatively analyze metabolite distribution in tissues with a high spatial resolution, thus providing molecular data in relation to cancer histopathology. The technique is ideally suited to study tissues molecular content and is able to provide molecular biomarkers or specific mass signatures which can be used in classification or the prognostic evaluation of tumors. Recently, it was shown that FFPE tissue samples are also suitable for metabolic analyses. This progress in methodology allows access to a highly valuable resource of tissues believed to widen and strengthen metabolic discovery-driven studies.
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