sepantronium bromide (PC-002) / Astellas, Cothera Biosci - LARVOL DELTA

Study of PC-002 (Sepantronium Bromide), a First-in-Class Inhibitor of Deubiquitinases (DUBs) Targeting Myc Degradation in Relapsed/Refractory c-Myc Rearranged High-Grade B Cell Lymphoma (HGBCL): Updated Phase 2 Results (ASH 2024) - P2 | "Background : C-Myc rearrangement is a hallmark of high-grade B-cell lymphoma (HGBCL) and Burkitt lymphoma (BL) [1], effective treatment for relapsed/refractory disease represents an unmet need. Conclusions : PC-002 monotherapy demonstrated high clinical activity in heavily pretreated BL patients with a good safety profile. Initial successful salvage attempt with the addition of Rit suggests that a SepB-Rit combination will lead to greater clinical benefit, and warrants further clinical investigation of the combination of PC002 with rituximab in patients with relapsed/refractory c-Myc driven Burkitt lymphoma or diffuse large B-cell lymphoma."

P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • BIRC5 • MYC

Integrative Spatial and Single-Cell Transcriptomics Uncovers Therapeutically Actionable Pathways in Embryonal Tumors with Multilayered Rosettes (EANO 2026) - "Our study highlights DNA damage response and anti-apoptotic pathways as actionable therapeutic targets in ETMRs and supports the potential use of DNA damage pathway inhibitors, alone or in combination, as a novel treatment strategy for this aggressive pediatric brain tumor."

Embryonal Tumor • Oncology

Decoding age-stratified clinical and molecular heterogeneity in male breast cancer through multiomic profiling. (PubMed, Chin J Cancer Res) - "GDSC-guided prioritization with PDO testing nominated sepantronium bromide (YM155) as a candidate vulnerability in YMBC...YMBC patients demonstrated inferior recurrence-free survival, neural signaling enrichment, an immune-cold microenvironment, and enriched NBPF10 mutations. These findings support age as a meaningful stratification variable in MBC risk assessment and treatment planning, and highlight the need for caution when considering treatment de-escalation in younger patients, while nominating YM155 as a candidate agent for prospective evaluation."

Heterogeneity • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Male Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • HER-2 • NBPF10

Survivin drives renal cell carcinoma tumorigenesis via proliferative and metabolic adaptation. (PubMed, Dis Model Mech) - "Unexpectedly, survivin depletion increased mitochondrial content while lowering oxygen consumption, indicating accumulation of dysfunctional mitochondria. Together, these findings identify survivin as a node between cell-cycle progression and mitochondria in RCC."

Journal • Clear Cell Carcinoma • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BIRC5 • CCND1

High-throughput screening identification of USP7 inhibitors reveals YM155 as a biologically active scaffold with in vivo antitumor efficacy. (PubMed, Biomed Pharmacother) - "Importantly, YM155 demonstrated significant tumor growth inhibition in lung and breast cancer mouse models, supporting its in vivo activity and pharmacological tractability in clinically relevant settings. Together, these findings expand the chemical space of USP7 inhibitors and identify YM155 as a hit for further optimization and mechanistic investigation toward USP7-targeted anticancer therapeutics."

Journal • Preclinical • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • FOXP3 • MYCN • PTEN • USP7

Pain-Related PANoptosis Gene Signature Predicts Prognosis and Guides Therapy in Oral Squamous Cell Carcinoma. (PubMed, Technol Cancer Res Treat) - "GSEA identified activated pathways like autophagy and chemokine signaling in high-risk patients.ConclusionsThe pain-related PANoptosis-gene model effectively stratifies OSCC patients by risk. Sepantronium bromide may represent a potential therapeutic candidate for high-risk patients; however, further experimental validation is required."

Biomarker • Gene Signature • Journal • Oncology • Oral Cancer • Pain • Squamous Cell Carcinoma • CA9 • IGLL5

Single-cell transcriptomics reveals the prognostic and immune infiltration significance of FOLFOX-bevacizumab treatment and lysine crotonylation characteristics in colon cancer. (PubMed, J Gastrointest Oncol) - "Colon cancer (CC), a malignant tumor originating from the colonic mucosal epithelium, frequently exhibits limited efficacy in advanced patients undergoing first-line FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil)-bevacizumab (FOLFOX-Bev) therapy due to resistance...Six categories of differential candidate drugs were screened (e.g., Erlotinib_1168, AZD3759_1915, Dasatinib_1079, and Sepantronium.bromide_1941)...The prognostic model, based on key genes (USP53/UACA/C7orf50/IDH2), accurately stratifies patient risk. This model provides novel insights for targeted therapy and immune-combination strategies in CC."

IO biomarker • Journal • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • IDH2

Development and Validation of a Prognostic Model for Cervical Cancer Based on Chlamydia trachomatis-Associated Transcriptional Signatures. (PubMed, Int J Womens Health) - "Drug sensitivity analysis identified BI-2536, SB505124, and Sepantronium bromide as potential therapeutic agents for high-risk patients. We established a novel prognostic model for CESC based on CT-related genes in an HPV-positive CESC background, which provides new insights into CT infection-associated immune regulation in CESC and individualized immunotherapy and targeted treatment strategies."

IO biomarker • Journal • Cervical Adenocarcinoma • Cervical Cancer • Cervical Squamous Cell Carcinoma • Infectious Disease • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD4

Stress granules as RNA triage hubs suppress extracellular vesicle secretion under oxidative stress in cancer. (PubMed, Proc Natl Acad Sci U S A) - "Pancancer transcriptomic analyses further show that Rab27A expression correlates with FOXO3a-dependent antioxidant programs, underscoring clinical relevance. These findings reveal that SGs actively reprogram RNA fate to tune vesicle output, establishing a redox-responsive mechanism by which cancer cells transiently suppress EV secretion to enhance survival."

Journal • Oncology • CD63 • FOXO3 • RAB27A

A layered double hydroxide nanocarrier enables YM155 delivery-induced PANoptosis and immunogenic activation in hepatocellular carcinoma. (PubMed, RSC Adv) - "Further immune profiling revealed enhanced dendritic cell maturation, pro-inflammatory macrophage polarization, and increased cytotoxic CD8+Granzyme B+ T-cell activation within the tumor microenvironment. Collectively, this LDH-based nanotherapeutic strategy enhances YM155 efficacy by coupling Survivin inhibition with PANoptosis activation and ICD-associated immune stimulation, providing a promising platform for hepatocellular carcinoma therapy."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • ANXA5 • CALR • CASP3 • CASP8 • CD8 • GZMB • HMGB1 • NLRP3

Whole-genome doubling drives immune evasion by silencing antigen presentation. (PubMed, Cancer Cell) - "PRC2 inhibition preferentially suppresses WGD+ tumor growth, enhances antigen presentation, and CD8+ T cell infiltration. Our results underscore metabolic and epigenetic alterations as critical drivers of WGD-associated immune escape."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • CD8 • IFNG

Survivin degrader 7I14 synergizes with docetaxel in castration-resistant prostate cancer by disrupting survivin dimerization and inducing its proteasome-dependent degradation (AACR 2025) - "In a PC-3 xenograft model, 7I14 at 15 mg/kg administered via IP twice/week effectively suppressed tumor growth and enhanced docetaxel's effects by degrading survivin, with no added toxicity, as assessed by body weight, white blood cell counts, and hemoglobin levels. Thus, targeting survivin's dimerization domain is a promising strategy for its degradation, and 7I10 and 7I14 have potential as single agents or in combination with docetaxel for treating metastatic CRPC."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BIRC5 • CASP3 • CASP9

Navitoclax, a Bcl-2/xL inhibitor, and YM155, a survivin inhibitor, in combination with carboplatin effectively inhibit ovarian cancer tumor growth (AACR 2025) - "Initial results showed that Omipalisib, Verteporfin, CA3, Mitoxantrone, Navitoclax, Venetoclax and YM155 had significant single drug activity in either the ALDH low or both the ALDH low/high cell populations... Our results suggest that the combination of Navitoclax/YM155/carboplatin has promise as a therapy for the treatment of OvCa."

Combination therapy • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BCL2 • CA3

Immune-associated genes as potential therapeutic targets in small cell lung cancer (AACR 2025) - "We identified AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, and AURKA genes as potential immune-related therapeutic targets for SCLC. In particular, high BIRC5 expression promotes SCLC progression and may influence the immune microenvironment of the tumor by affecting monocytes."

IO biomarker • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • AURKA • AURKB • GLI2 • PCNA • PD-L1 • TOP2A • TYMS • UBE2C

Molecular Actions of Sepantronium bromide (YM155) on Survivin-Dependent Cell Death in Cancer and Beyond. (PubMed, Chem Biol Interact) - "Beyond oncology, emerging findings have repositioned YM155 as a probe to interrogate survivin-regulated processes in vascular and immune pathologies. By bridging molecular and clinical evidence, this review contextualizes YM155 within the broader landscape of targeted small molecules, emphasizing its value as a model for developing next-generation survivin modulators and precision-based therapeutic strategies."

Journal • Review • Hematological Disorders • Hematological Malignancies • Oncology

Itaconate-Related Gene Signatures as Prognostic Markers in Colon Cancer: Insights From Transcriptomic and Spatial Analysis. (PubMed, Hum Mutat) - "Drug sensitivity analysis identified four potentially effective drugs, such as sepantronium bromide, which had better effects on high-risk patients. This study provides a theoretical basis and new targets for precise prognosis and stratified treatment of colon cancer."

Biomarker • Gene Signature • IO biomarker • Journal • Tumor mutational burden • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD36 • CDKN2A • CXCL1 • INHBB • SCARB1 • TIMP1 • TMB

Whole-genome doubling promotes immune evasion in TNBC by epigenetically silencing antigen presentation pathways through PRC2 activity. (SABCS 2025) - "Through single-cell profiling, we found that WGD+ cancer cells exhibit impaired antigen presentation, driven in part by a reduced response to IFN-γ and epigenetic silencing of MHC class I transcriptional regulators via the PRC2 complex.Treatment with a PRC2 inhibitor preferentially inhibited WGD+ tumor growth, restored antigen presentation, and enhanced CD8⁺ T cell infiltration. These findings suggest that combined inhibition of PRC2 and PD-1 represents a promising therapeutic approach for WGD+ breast cancers."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer • CD8 • HER-2 • IFNG

Strategic trimodal therapy enhances radiation-induced abscopal response in renal cancer. (PubMed, J Transl Med) - "This study presents a novel and effective strategy to induce the abscopal effect through a synergistic combination of targeted drug delivery, radiotherapy, and immunotherapy. The approach offers strong translational potential for improving radioimmunotherapy outcomes in renal and potentially other immunogenic cancers."

Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD163 • CD8 • IL2

From bioinformatics to clinical translation: BIRC5 as a pivotal diagnostic biomarker and therapeutic target for NAFLD-driven HCC. (PubMed, Cell Biol Toxicol) - "This study proposes BIRC5 as a therapeutic target and diagnostic biomarker, offering perspectives for HCC diagnosis and treatment of HCC. These results underscore the importance of BIRC5 in halting NAFLD-HCC progression and provide valuable insights for future clinical applications."

Biomarker • Journal • Addiction (Opioid and Alcohol) • Fibrosis • Gastroenterology • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • BIRC5 • CCNB1 • CDK1 • TOP2A

Mapping the Progression of Therapy-Induced Senescence to Therapy Tolerance: An Evolutionarily Conserved Mechanism for Optimizing Cancer Treatment with Senotherapeutics. (PubMed, ACS Pharmacol Transl Sci) - "However, this was most effective within a specific time window after TIS induction. We suggest that the timely use of senotherapeutics could improve the effectiveness of anticancer drugs in clinical settings."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TGFB1

YM155 Inhibition of Survivin Enhances Carboplatin Efficacy in Metastatic Castration-Resistant Prostate Cancer. (PubMed, Pharmaceuticals (Basel)) - "YM155 (Sepantronium bromide) suppresses survivin expression and has demonstrated antitumor activity in preclinical models. The integration of clinical and functional data provides translational support for combining the survivin inhibitor YM155 with platinum-based therapy. These results warrant further validation in larger patient cohorts and in vivo models."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Multiplexed Transcriptomics for Screening Drug Combinations and Defining the Mechanism of Action of HCC Therapeutics at Single-Cell Resolution. (PubMed, Cell Prolif) - "A gene regulatory network analysis highlighted JUN as a key regulator mediating proliferation inhibition, primarily active in the apoptotic cell subcluster. These findings illustrate how integrating high-throughput screening with mechanistic dissection can accelerate the discovery of targeted drug combination therapies, and offer a blueprint for precise interventions using pathway vulnerabilities and cellular heterogeneity in HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Integrating bulk and single-cell RNA sequencing analysis to reveal characterization of mechanical stimulus-related genes and prognostic signatures in breast cancer. (PubMed, Breast Cancer Res) - "We developed a pioneering prognostic signature incorporating MSRGs in breast cancer, with a particular focus on mechanical stimuli may influence breast cancer prognosis by remodeling the immune microenvironment. The findings highlighted the importance of personalized treatment strategies and provide new insights into the role of mechanical forces in breast tumor biology."

Journal • Breast Cancer • Oncology • Solid Tumor

Single-Cell Multi-Ome Analysis Reveals Novel Molecular Mechanisms Underlying Subclonal Response to Survivin Inhibition in Relapsed/Refractory Multiple Myeloma (ASH 2023) - "An earlier study has shown that YM155 enhances daratumumab-mediated cellular lysis of multiple myeloma cells. Our RNAseq and CyTOF results thus suggest a potential basis of synergy between YM155 with immunotherapies approved for myeloma, which we will test further. Our approach thus integrates in silico prediction with single-cell multi-ome analysis to identify molecular mechanisms potentially underlying subclonal response to novel combination therapy candidates (secDrugs) for the treatment of RRMM."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • ATF3 • BIRC5 • CD81 • CDC37 • DDIT3 • PD-L1

Treatment of Relapsed/Refractory Hgbcl and Bukitt's Lymphoma with c-Myc Rearrangement: A Multi-Center, Open-Label, Phase 2 Study of PC-002 (SepB), a First-in-Class Deubiquitinase Inhibitor Inducing Myc Degradation (ASH 2023) - P2 | "PC-002 (also known as Sepantronium Bromide, or SepB) is a small molecule previously identified as a survivin suppressant with antitumor activity against a range of tumor types... At the time of abstract submission, the 1st cohort (3.6 mg/m2/day) of 3 patients have completed at least four cycles of treatment. PC-002 is generally well-tolerated at 3.6 mg/m2/day and progression to Cohort 2 at a dose of 4.8 mg/m2/ day was approved by the Safety Review Committee. Two patients with relapsed/refractory Burkitt Lymphoma at the starting dose of 3.6 mg/m2/day achieved a confirmed PR."

Clinical • P2 data • Anemia • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • BIRC5 • MYC