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- Understanding the differentiation syndrome in acute promyelocytic
leukemia: a comprehensive updated review-
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Abstract: The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Differentiation syndrome (DS) is a common and potentially life-threatening condition that was initially described with the induction therapy of targeted agents in acute promyelocytic leukemia (APL). DS is typically marked by symptoms such as fever, difficulty breathing, low blood pressure, weight gain, fluid buildup in the pleural or pericardial cavities, and acute kidney failure. The incidence of DS in APL patients varies from 2 to 27% reflecting the discrepancies in diagnostic criteria, in various treatment protocols, and sometimes the use of preventive treatments. Corticosteroids, with or without cytoreductive therapy, should be initiated immediately upon suspicion of DS to mitigate related morbidity and mortality. In cases of severe DS, targeted anti-leukemic therapy should be halted. This review will cover the pathogenesis of DS, its clinical presentations, diagnostic criteria, management approaches, and the importance of implementing prospective tracking in clinical trials.
PubDate: 2025-06-25
- Research progress on cancer-related epigenetic switches
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Abstract: The dysregulation of cellular epigenetic machinery has been established as a fundamental driver of oncogenesis. This recognition has propelled cancer epigenetics to the forefront of biomedical research, particularly regarding the mechanistic characterization of epigenetic switching events. These molecular switches represent critical regulatory nodes in the malignant transformation. The epigenetic switch is a complex structure formed through interactions between nucleic acid–protein complexes or protein–protein interaction complexes and specific DNA fragments. Triggered by a priming event, this molecular apparatus can reversibly activate or repress the transcription of multiple downstream genes. The inherent reversibility of these epigenetic switches presents novel therapeutic opportunities for targeted cancer intervention. Consequently, this review provides a systematic analysis of cancer-associated epigenetic switches identified in the past decade. Graphical Abstract
PubDate: 2025-06-13
- Clinical characterizations, management, and prognosis in immune checkpoint
inhibitor-induced myelitis-
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Abstract: The expanding clinical application of immune checkpoint inhibitors (ICIs) has led to increasing recognition of neurological immune-related adverse events, among which myelitis represents a rare but clinically significant complication. Currently, most available data come from case reports or small case series, highlighting the need for comprehensive characterization. Our study systematically analyzed the clinical features of ICI-induced myelitis to improve diagnostic and therapeutic approaches. Through a comprehensive literature review up to February 28, 2025, we identified and analyzed 36 cases of ICI-associated myelitis from 27 publications. The study cohort had a median age of 58 years (range 16–81) with male predominance (58.3%). Clinical presentations included isolated myelitis (63.9%) and multifocal neurological involvement (36.1%), most commonly manifesting meningoencephalomyelitis/encephalomyelitis. The median time to symptom onset was 2 months (range 0.3–8) after treatment initiation, with a median of 4 treatment cycles (range 1–51). The most frequently associated malignancies were melanoma and lung cancer, with programmed cell death protein-1 inhibitor being the most commonly used regimen (69.4%). Diagnostic evaluation revealed longitudinally extensive spinal cord lesions (≥ 3 vertebral segments) in 75.0% of patients, along with frequent inflammatory cerebrospinal fluid abnormalities. Neural autoantibodies were detected in 33.3% of cases. Treatment strategies predominantly involved corticosteroids (97.2%) and ICI discontinuation (91.7%). While most patients (72.2%) showed improvement, relapses occurred in 30.6% of cases. These findings emphasize the importance of early recognition and prompt immunosuppressive therapy for ICI-induced myelitis.
PubDate: 2025-06-09
- A novel CDK4 inhibitor for myeloid protection in chemotherapy-treated
triple-negative breast Cancer-
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Abstract: Despite advances in cancer treatment, chemotherapy remains a cornerstone of clinical practice. However, its efficacy is often compromised by dose-limiting haematologic toxicities. Recent strategies aim to enha...
PubDate: 2025-06-06
- Clinical features, treatment, and outcomes of anti-PD-L1 induced psoriasis
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Abstract: This study focuses on rare immune-mediated psoriasis induced by anti-PD-L1 drugs. Given that its clinical features have not been fully defined, the aim is to clarify the clinical manifestations, treatment, and...
PubDate: 2025-06-06
- Approval of high-benefit oncology drugs in Japan: utilization of expedited
regulatory pathways for the accelerated approved anticancer drugs-
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Abstract: Early access to promising new drugs with superior efficacy compared to existing treatments is globally sought after. To facilitate such access, regulatory authorities in each country have implemented special r...
PubDate: 2025-06-04
- A phase I study of liposomal Irinotecan (ONIVYDE®) in combination with
TAS-102 (LONSURF®) in refractory solid tumors-
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Abstract: Onivyde, a liposome-encapsulated irinotecan, is used for advanced pancreatic, while TAS-102 (trifluridine/tipiracil) is indicated for metastatic colorectal and gastric cancers. This study aims to determine the...
PubDate: 2025-06-04
- Efficacy and safety of orelabrutinib combined with rituximab and high dose
methotrexate in primary or secondary central nervous system diffuse large
B-cell lymphoma: a retrospective analysis-
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Abstract: Central nervous system lymphoma (CNSL) are mainly diffuse large B-cell lymphomas (DLBCLs). Orelabrutinib is a second-generation Bruton’s tyrosine kinase (BTK) inhibitor and has shown single-agent activity in CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib combined with rituximab and high dose methotrexate (ORM) regimen in the treatment of patients with CNSL. We retrospectively analyzed data from CNSL patients treated with ORM regimen at Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University from April 2021 to October 2023. Patients receiving rituximab plus high-dose methotrexate (RM regimen) from June 2017 to January 2024 were identified as the control group. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A total of 32 patients were identified: 14 patients in the ORM group and 18 in the RM group. CR rates were 84.6% in the ORM group and 44.4% in the RM group (P = 0.032). Median PFS was 18.6 months in the RM group and 26.3 months in the ORM group (P = 0.133). Median OS was 34.1 months in the RM group and has not yet been reached in the ORM group (P = 0.041). Patients in the ORM group showed a higher 2-year OS rate than those in the RM group (82.1% vs. 57.5%). No grade 5 AE was reported in both groups. The incidence of grade 3–4 AE was comparable between the two treatment groups. ORM regimen was effective and well-tolerated in patients with CNSL. This combination therapy provides a new potential therapeutic strategy for patients with CNSL.
PubDate: 2025-05-31
- The recombinant anti-MET/EpCAM bispecific antibody fragment: a promising
novel therapeutic approach for breast cancer treatment-
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Abstract: Our study aims to target Met and EpCAM to inhibit angiogenesis in breast cancer, particularly triple-negative breast cancer (TNBC). We have developed a new bispecific antibody that targets both MET and EpCAM, which are commonly overexpressed in tumor cells. This antibody aims to reduce tumor cell proliferation and spread. After cloning and expressing the anti-Met/EPCAM sequence in Escherichia coli, we confirmed its accuracy through Western blot analysis. Flow cytometry indicated its binding activities to MET and EPCAM on MDA-MB-231 and MCF-7 cell lines. Our antibody showed anti-proliferative potential as indicated by apoptosis and MTT assay, leading to the inhibition of migration and invasion in breast cancer cell lines. After conducting a thorough analysis of cytokine production, we discovered that our bispecific antibody effectively influenced the levels of IL-8 and IL-6. These cytokines play crucial roles in angiogenesis and the progression of breast cancer. These findings indicate that our bispecific antibody holds promise as a potential therapy for triple-negative breast cancer. It has the potential to impede the formation of new blood vessels in tumors, thus restraining their growth and spread.
PubDate: 2025-05-30
- Orelabrutinib combined with rituximab and high-dose methotrexate as
induction therapy in newly diagnosed primary central nervous system
lymphoma-
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Abstract: Objective Limited treatment options for primary central nervous system lymphoma (PCNSL) highlight the need for alternative therapies. This study evaluated orelabrutinib (O) and rituximab (R), plus high-dose methotrexate (M) (ORM), as a potential induction therapy for newly diagnosed PCNSL. Methods Patients received six cycles of 150 mg/day orelabrutinib, 375 mg/m2 rituximab, plus 3.5 g/m2 methotrexate every 3 weeks, followed by autologous hematopoietic stem cell transplantation and orelabrutinib maintenance. The primary endpoint was the overall response rate (ORR) at the end of induction therapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results From October 21, 2020, to October 22, 2024, 28 patients were treated and evaluated for efficacy and safety analyses. At the end of induction therapy, the ORR was 71.4% (95% CI, 51.3–86.8), including 16 (57.1%) complete and 4 (14.3%) partial responses. At a median follow-up of 21.6 months, the median PFS was 35.3 months (95% CI, 8.4–not evaluable), and the median OS was not reached, with PFS and OS rates of 64.3% and 96.3% at 1 year, 64.3% and 90.9% at 2 years, and 45.9% and 82.7% at 3 years, respectively. All 28 (100%) patients experienced treatment-related adverse events (TRAEs) of any grade. Grade 3 TRAEs occurred in seven (25.0%) patients, including five (17.9%) leukopenia, one (3.6%) thrombocytopenia, and one (3.6%) diarrhea. No other Bruton’s tyrosine kinase inhibitor-related off-target toxicities (e.g., atrial fibrillation/flutter) or TRAE-related deaths were observed. Conclusion The ORM induction regimen showed anti-tumor activity with a favorable safety profile, offering a potential therapeutic strategy for newly diagnosed PCNSL. Clinical trial registration: ClinicalTrials.gov: NCT05600660.
PubDate: 2025-05-27
- Peptide YY fragment PYY1-36 disrupts mitochondrial biogenesis via
RBM43-dependent PGC-1α translation inhibition-
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Abstract: Mitochondrial dysfunction is a key driver of cancer progression, with therapies increasingly targeting metabolic weaknesses. Peptide YY (PYY), a gastrointestinal hormone, regulates cellular activity, but its influence on mitochondrial health in lung cancer remains poorly understood. We explored how PYY1-36, a bioactive fragment of PYY, affects mitochondrial stability in NCI-H1581 lung cancer cells. Using dose–response experiments, we measured oxidative stress by tracking lactate dehydrogenase (LDH) release, mitochondrial ROS levels, and oxidative DNA damage (8-OHdG). Energy production was evaluated through ATP levels, oxygen consumption rates (OCR), and Complex I activity. We also analyzed mitochondrial biogenesis markers (NRF1, TFAM, PGC-1α) and the RNA-binding protein RBM43 via qPCR and immunoblotting. Dose-dependent tests showed that PYY1-36 triggers mitochondrial oxidative damage, marked by higher LDH release and ROS spikes. These changes aligned with sharp drops in ATP production and disrupted respiratory function. Notably, PYY1-36 reduced mitochondrial mass and biogenesis, supported by weaker MitoTracker Red signals and lower mtDNA/nDNA ratios. Key regulators NRF1 and TFAM were strongly suppressed, pointing to widespread mitochondrial failure. Intriguingly, PYY1-36 blocked PGC-1α protein synthesis without altering mRNA levels, suggesting a post-transcriptional control mechanism. PYY1-36 also boosted RBM43 levels. Knocking down RBM43 reversed PYY1-36’s effects on PGC-1α and mitochondrial health. Our findings reveal RBM43 as a central player in PYY1-36-induced mitochondrial dysfunction through its suppression of PGC-1α translation. Targeting RBM43 could unlock new strategies to tackle metabolic chaos in lung cancer. Graphical Abstract
PubDate: 2025-05-22
- Medulloblastoma associated with Lynch syndrome: a case report of germline
MLH1 variant and tumor molecular characterization-
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Abstract: Lynch syndrome (LS) is an autosomal autosomal dominant inherited disease characterized by impaired DNA mismatch repair (dMMR), resulting in an elevated susceptibility to various types of cancer. The incidence of brain cancers in individuals with LS ranges from 2 to 8%, with the highest risk observed for glioblastoma, astrocytoma, and oligodendroglioma. Medulloblastoma (MB) with Lynch syndrome, a common malignant brain tumor in children, is exceedingly rare. In this case, we present a case of a pediatric patient diagnosed with MB based on clinical and pathological findings, which was further characterized as an TP53-mutant, SHH-activated MB through next-generation sequencing (NGS), and methylation profiling. His tumor was found to harbor a somatic MSH2 mutation and a suspected pathogenic germline MLH1 heterozygous variant. Simultaneously, the tumor exhibited microsatellite instability-high (MSI-H) and an exceptionally elevated tumor mutation burden (TMB = 297.17 Mut/Mb). The presence of the MLH1 germline variant in the patient’s mother and maternal grandmother was confirmed by sequencing, and the patient’s maternal grandmother had a history of colorectal cancer. Ultimately, the patient was diagnosed with MB associated with LS. This case is the third case of LS with medulloblastoma, which contributes additional evidence to the cancer spectrum associated with LS and presents a novel avenue for patient treatment.
PubDate: 2025-05-19
- TP53 and DNA-PK as potential biomarkers for enhanced efficacy of Olaparib
in colorectal cancer-
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Abstract: Olaparib is selected based on the presence of BRCA mutations in patient populations; however, further investigation is still required regarding its effect on restoring homologous recombination (HR) through the inactivation of non-homologous end joining (NHEJ). Therefore, identifying regulators of NHEJ could increase the sensitivity of cancer cells to Olaparib by inhibiting DNA damage repair is a major focus of current research. Loss of DNA-dependent protein kinase (DNA-PK), which is a major components of NHEJ, compromises DNA damage repair, and the resulting increase in DNA damage burden may heighten reliance on poly (ADP-ribose) polymerase (PARP)-dependent DNA repair in cancer cells, rendering them more susceptible to PARP inhibitor therapy. However, DNA-PK alone is not sufficient to enhance the effectiveness of Olaparib, so various adjuvant and combination therapies are being explored. We classified colorectal cancer (CRC) cells based on their sensitivity to Olaparib and found that they were categorized according to TP53 status. Here, we examine the role of DNA-PK in the response to Olaparib, emphasizing its relationship with TP53 status. Our findings indicate that the inhibition of DNA-PK enhances sensitivity to Olaparib and induces phosphorylation of p53 exclusively in cells with TP53 wild-type (WT). Furthermore, using CRC patient-derived cells (PDC) and patient-derived xenograft (PDX) model, we show that the sensitivity of Olaparib is determined TP53 and DNA-PK genotypes. These findings highlight TP53 and DNA-PK as potential predictive biomarkers for optimizing PARP inhibitor-based therapy in CRC.
PubDate: 2025-05-16
- MicroRNA nanoformulation: a promising approach to anti-tumour activity
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Abstract: Cancer is a major cause of morbidity and mortality, making it one of the most debilitating diseases in our time. Despite advancements in therapeutic strategies, the development of chemoresistance and the occurrence of secondary tumours pose significant challenges. While several promising anti-tumour agents have been identified, their clinical utility is often limited due to toxicity and associated side effects. MicroRNAs (mi-RNAs) are critical regulators of gene expression, and their altered levels are closely linked to cancer development and progression. Although some microRNAs have shown potential as biomarkers for cancer detection, their integration into routine clinical practice has yet to be realized. Numerous candidate microRNAs exhibit therapeutic potential for cancer treatment; however, further research is needed to create efficient, patient-compliant, and customized drug delivery systems. In recent decades, various nanotechnology platforms have successfully transitioned to clinical trials, particularly in the field of RNA nanotechnology. Several RNA nanoparticles have been developed to address key challenges in vivo for targeting cancer, demonstrating favourable biodistribution characteristics. Studies have shown that RNA nanoparticles, characterized by precise stoichiometry and homogeneity, can effectively target tumour cells while avoiding aggregation in normal, healthy tissues following systemic injection. Animal models have demonstrated that RNA nanoparticles can deliver therapeutics such as siRNA and anti-microRNA, effectively inhibiting tumour growth. Using nanoparticles conjugated with antibodies and/or peptides enhances the targeted delivery and sustained release of microRNAs and anti-microRNAs, which may reduce the required therapeutic dosage and minimize systemic and cellular damage. This review focuses on developing microRNA nanoformulations to improve cellular uptake, bioavailability, and accumulation at tumour sites, assessing their potential anti-tumour efficacy against various types of malignancies. The significance of these advancements in clinical oncology cannot be overstated. Graphical Abstract
PubDate: 2025-05-14
- Evaluation of anti-leukemic activity and underlying mechanisms of the
novel GSPT1 degrader AB138 in acute myeloid leukemia-
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Abstract: Acute myeloid leukemia (AML) is a relapsing and drug-resistant hematologic malignancy. We report AB138, a novel molecular glue degrader that recruits G1-to-S phase transition protein 1 (GSPT1) to cereblon (CRBN). In AML cell lines, AB138 induces rapid, sustained GSPT1 degradation. qPCR and immunoblotting revealed activation of the integrated stress response, as evidenced by eIF2α phosphorylation and the upregulation of ATF3 and CHOP. The subsequent depletion of the oncoproteins MCL1 and c-Myc coincides with the accumulation of cleaved caspase-3 and cleaved PARP and marked apoptosis. Flow cytometric analysis confirmed pronounced S-phase arrest together with an increase in the number of Annexin V–positive cells. Oral administration of AB138 significantly reduces the tumor burden in an MV-4–11-Luc xenograft model without overt toxicity. These findings demonstrate that efficient GSPT1 degradation by AB138 promtoes integrated stress signaling and downregulates the survival-promoting BCL-2 family member MCL1 and the oncogenic driver c-Myc, leading to potent antileukemic activity in vitro and in vivo and supporting further development of AB138 for AML therapy.
PubDate: 2025-05-14
- Unraveling BOLD-100 synergistic potential in pleural mesothelioma
treatment: an in vitro study-
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Abstract: Pleural mesothelioma (PM) is a rare cancer affecting the pleural layer on the body’s serosal surfaces. Exposure to asbestos fibers, a naturally occurring fibrous material with insulating characteristics, contributes to PM’s prevalence. PM has a long latency period, making major surgery ineffective and necessitating systemic treatment. Despite the progress of mesothelioma treatment, the median survival is very poor; so, there is a strong need to explore new therapeutic approaches. This study explores the use of BOLD-100, a novel therapeutic drug that targets GRP78, a protein overexpressed in PM cells. BOLD-100, a ruthenium-based small molecule therapeutic drug, is being investigated for the treatment of advanced gastrointestinal malignancies in conjunction with chemotherapy. Our aim is to investigate cellular responses of several PM cell lines to a regimen that includes BOLD-100 in addition to other commonly used treatments. BOLD-100 is a ruthenium-based anticancer therapeutic.
PubDate: 2025-05-08
- Novel GPC3 N-terminal bispecific antibody exhibits dual anti-tumor effect
against tumor cells-
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Abstract: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with poor prognosis and limited treatment options, particularly in advanced stages. Glypican-3 (GPC3) has emerged as a promising therapeutic target, but existing antibodies primarily bind its C-terminal region, where glycosylation can mask epitopes and compromise efficacy. To address this limitation, we focused on the GPC3 N-terminal region, which offers better accessibility and potential for tumor signaling regulation. We developed Pro-12, a high-affinity humanized IgG1 antibody targeting the 25–45 peptide of the GPC3 N-terminus, avoiding glycosylation interference while modulating tumor pathways. Building on Pro-12, we engineered a GPC3/CD3 bispecific antibody (BsAb) using CrossMab and Knob-into-Hole technologies. This BsAb demonstrated dual anti-tumor effects by activating immune cells and inhibiting both the Wnt/β-catenin and PI3K/AKT pathways, achieving outcomes typically requiring tri-specific antibodies. Our findings highlight the GPC3 N-terminal region as a novel therapeutic target and introduce a promising bispecific antibody approach for the treatment of GPC3-positive HCC.
PubDate: 2025-05-01
- An investigation of extended-interval dosing of atezolizumab in Japanese
patients with advanced solid tumors: safety and pharmacokinetics of a dose
of 1680Â mg every 4 weeks-
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Abstract: In Japan, atezolizumab is indicated for several cancers at a dose of 1200 mg every 3 weeks or 840 mg every 2 weeks. This open-label study (jRCT2031220151) aimed to assess an atezolizumab monotherapy dose of 1680 mg every 4 weeks (Q4W) in Japanese patients ≥ 18 years of age with advanced or recurrent solid tumors that were not responsive to standard treatment. The primary endpoints were tolerability, safety, and pharmacokinetics (PK). Secondary endpoints included overall response rate and progression-free survival. Overall, 21 patients were enrolled in the study. The median age for males (42.9%) and females (57.1%) was 61 years, and the median (range) treatment duration was 29.0 (1–224) days. During the dose-limiting toxicity (DLT) evaluation period, 3 out of 6 (50.0%) patients experienced at least 1 adverse event, although no DLTs or deaths were experienced. The PK profile of atezolizumab 1680 mg Q4W monotherapy in cycle 1 after 30 min of administration had an arithmetic mean maximum concentration (standard deviation [SD]) of 699 (146) µl/mL and a mean minimum concentration (SD) 133 (46.0) µl/mL, The mean (SD) area under the curve was 7180 (1340) days‧µg/mL. These data show that atezolizumab 1680 mg Q4W monotherapy was well tolerated in Japanese patients with no new safety concerns, suggesting that this less frequent dosing regimen could have the potential to offer greater flexibility and convenience for patients and caregivers.
PubDate: 2025-05-01
- Targeting Myc through BET-PROTAC elicits potent anti-lymphoma activity in
diffuse large B cell lymphoma-
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Abstract: Diffuse large B cell lymphoma (DLBCL) presents a great challenge in the clinic due to its poor prognosis. Prior research has identified c-Myc as a promising therapeutic target in DLBCL; however, direct targeting of c-Myc protein has proven challenging. The bromodomain and extraterminal (BET) protein family, which acts as transcriptional and epigenetic regulators, plays a crucial role in super-enhancer organization and transcriptional regulation of oncogenic drivers like c-Myc, offering an alternative approach. Recently developed BET proteolysis targeting chimera (PROTAC) compounds can rapidly and effectively degrade BET proteins and potentially offer a more durable effect than traditional BET inhibitors. In this work, we compared the anti-tumor activity of a BET PROTAC, ARV-825, with a BET inhibitor, JQ1, in DLBCL. Cell proliferation was assessed by CCK-8 assay, apoptosis was evaluated by Annexin V/PI staining, and the cell cycle was analyzed by staining DNA with propidium iodide (PI). Western blotting was used to determine the expression levels of BET family proteins and its downstream regulatory gene c-Myc, and the in vivo SCID mouse model implanted with SU-DHL-4 cells was used to analyze the in vivo drug efficacy. Our results showed that ARV-825 was superior to JQ1 in inhibiting DLBCL cell proliferation, inducing apoptosis, promoting cell cycle arrest, and prolonging survival. Notably, ARV-825 was more effective at downregulating c-Myc and BET protein levels than JQ1 in both in vitro and in vivo experiments. These evidences suggest that BET-PROTACs may offer a promising novel strategy for the clinical treatment of DLBCL.
PubDate: 2025-05-01
- Safety, tolerability, and preliminary efficacy of nadunolimab, an anti-IL-
1 receptor accessory protein monoclonal antibody, in combination with
pembrolizumab in patients with solid tumors-
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Abstract: Interleukin (IL)-1 signaling has an essential role in tumor progression and immunosuppression and is linked to acquired resistance to anti-PD-1/PD-L1 treatment. Nadunolimab is an IL1RAP (IL-1 receptor accessory protein)-targeting antibody that blocks IL-1α/IL-1β signaling and has enhanced antibody-dependent cellular cytotoxicity. We investigated the safety and preliminary efficacy of nadunolimab with pembrolizumab in patients with metastatic solid tumors who had progressed on previous checkpoint inhibitor treatment, suggesting acquired checkpoint inhibitor resistance (NCT04452214). This phase 1b trial enrolled patients with metastatic disease who had exhausted or declined standard-of-care alternatives. Patients received nadunolimab (5 mg/kg) and standard-dose pembrolizumab. The primary objective was to assess safety. Secondary objectives were anti-tumor response as per iRECIST, pharmacokinetics, and changes in immune mediators. Fifteen patients with stage IV cancer (head and neck squamous cell carcinoma, non-small cell lung cancer, melanoma) entered the trial. Grade ≥ 3 adverse events were reported for 7 patients (47%). There was one dose-limiting toxicity of febrile neutropenia. The most frequent grade ≥ 3 adverse event was dysphagia (two patients). Seven patients (47%) had reductions in target lesion size. Median iPFS was 3.4 months (95% CI 1.4–8.6). Median OS was 19.7 months (95% CI 4.3–28.7) with 67% 1-year survival. Survival was significantly longer in patients with higher baseline tumor infiltration of CD163 + macrophages and natural killer cells and in patients with reduced on-treatment circulating IL-6 levels or neutrophil-to-lymphocyte ratio. Nadunolimab with pembrolizumab had an acceptable safety profile, and prolonged disease control was observed in a subset of patients. The results support further development of nadunolimab in combination with checkpoint inhibitors.
PubDate: 2025-05-01
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