sabutoclax (ONT-701) / Sanford-Burnham Medical Research Institute, Pfizer - LARVOL DELTA

Revolutionizing prognosis: Introducing cell death index (CDI) as a powerful prognostic tool for CSCC patients. (PubMed, Environ Toxicol) - "This investigation constructed a novel effective prognostic indicator of CDI in patients with CSCC and identified potential genes associated with cell death that could be targeted for prognosis and treatment of CSCC."

Journal • Cervical Cancer • Cervical Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Pan-cancer landscape of disulfidptosis across human tumors. (PubMed, Heliyon) - "Additionally, tumors with low disulfidptosis score exhibited higher sensitivity to a few small molecular compounds, e.g., Sabutoclax, PRIMA-1MET, BIBR-1532, and Elephantin. Knockdown of disulfidptosis gene GYS1 effectively hindered tumor progression. Collectively, our findings depict a pan-cancer map of disulfidptosis to inform functional and therapeutic research."

Journal • Pan tumor • Oncology • Solid Tumor

Explore the expression of mitochondria-related genes to construct prognostic risk model for ovarian cancer and validate it, so as to provide optimized treatment for ovarian cancer. (PubMed, Front Immunol) - "In terms of drug sensitivity, the high-risk group was more sensitive to vinblastine, Acetalax, VX-11e, and PD-0325901, while the low-risk group was more sensitive to Sabutoclax, SB-505124, cisplatin, and erlotinib. The prognostic risk model of ovarian cancer associated to mitochondrial genes built on the basis of public database better evaluated the prognosis of ovarian cancer patients and guided individual treatment."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Oncology • Ovarian Cancer • Solid Tumor • TMB

Establishment of a prognostic model for pancreatic cancer based on mitochondrial metabolism related genes. (PubMed, Discov Oncol) - "By utilizing a gene signature associated with mitochondrial metabolism, a prognostic model has been established which could be a highly efficient method for predicting the outcomes of PAAD patients."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • TP53

Hypoxia-based critical gene biomarkers as prognostic reporters for gastric adenocarcinoma. (PubMed, Environ Toxicol) - "The Hypoxia-score proves to be a valuable tool for assessing the prognosis of gastric cancer patients and guiding drug treatments, providing significant guidance for clinical diagnosis and treatment in the context of gastric cancer."

Biomarker • IO biomarker • Journal • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Coordination-Driven Self-Assembly of Biomedicine to Enhance Photodynamic Therapy by Inhibiting Proteasome and Bcl-2. (PubMed, Adv Healthc Mater) - "Herein, a self-delivery biomedicine (designated as BSC) is developed by the self-assembly of Bortezomib (BTZ), Sabutoclax (Sab) and Chlorin e6 (Ce6). Of special note, the coordination-driven self-assembly of BSC is pH-responsive, which could be disassembled for controlled drug release upon tumor acidic microenvironment. This study would expand the applicability of self-delivery nanomedicine with sophisticated mechanisms for tumor treatment."

Journal • Lymphoma • Oncology • BCL2

A novel strategy for precise prognosis management and treatment option in colon adenocarcinoma with TP53 mutations. (PubMed, Front Surg) - "Moreover, we identified SGPP1, RHOQ, and PDGFRB as potential targets for TP53-mutant COAD, and illuminated that the high-risk patients might benefit from IGFR-3801, Staurosporine, and Sabutoclax...Besides, we identified novel therapeutic targets and potential sensitive agents for TP53-mutant COAD with high risk. Our findings provided not only a new strategy for prognosis management but also new clues for drug application and precision treatment in COAD with TP53 mutations."

Journal • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Inflammatory Arthritis • Oncology • Solid Tumor • FCGR3A • PDGFRB • TP53

Profiling of a novel circadian clock-related prognostic signature and its role in immune function and response to molecular targeted therapy in pancreatic cancer. (PubMed, Aging (Albany NY)) - "We successfully established and verified a novel circadian clock-related gene signature, which could stratify patients with different risk and be reflective of the therapeutic effect of molecular targeted therapy. Our findings could incorporate the pharmacological modulation of circadian clock into future therapeutic strategies."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ARNTL • CD8 • CDK1 • KLF10

Anticancer effects of putative and validated BH3-mimetic drugs in head and neck squamous cell carcinomas: An overview of current knowledge. (PubMed, Oral Oncol) - "One phase-II clinical trial assessing gossypol (combined with docetaxel) was found. The remaining 39 preclinical studies investigated cell lines and/or xenograft models involving the use of six validated BH3-mimetics (A-1210477, A-1331852, ABT-737, navitoclax, S63845, venetoclax) and six putative BH3-mimetics (ApoG2, gossypol, obatoclax, sabutoclax, TW-37, and YC137)...In conclusion, although clinical data are still insufficient to evaluate the anticancer effects of BH3-mimetics in head and neck squamous cell carcinomas, promising results in preclinical settings were observed concerning induction of cell death and inhibition of tumour growth. Therefore, further clinical trials are highly encouraged."

Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] REVEALING TRANSCRIPTOME DEREGULATION COMPLEXITY IN MULTIPLE MYELOMA (EMN 2021) - "The SKMM2 MM cell line, harboring t(11;14), del(CYLD) was highly sensitive to Venetoclax...Of note, these latter resulted sensitive to Sabutoclax, a panBCL2-axis inhibitor... Our study showed a link between the genomic archi- tecture and transcriptome in MM, where CNAs and CRs had a stron- ger impact on expression than gene mutations. Within these lattes UPON GENOMIC HS ones need further testing as they may represent future treatment targets. Moreover, the mutational status is crucial since, due to the transcriptomic consequences of bi-allelic events which provides bio- logical basis for the observed prognostic impact of “double-hit” MM."

IO biomarker • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • BCL2L1 • BRAF • KRAS • NRAS • TP53

[VIRTUAL] Revealing Transcriptome Deregulation upon Genomic Complexity in Multiple Myeloma (ASH 2020) - "The SKMM2 MM cell line, harboring t(11;14), del(CYLD) e NOXAamp was highly sensitive to Venetoclax...Of note, these latter resulted sensitive to the pan-BCL2 axis inhibitor Sabutoclax...Moreover, the mutational status is crucial since, while mono-allelic events are often of little transcriptional value, compound heterozygosity carries a huge influence on transcriptomic which provides biological basis for the observed prognostic impact of “double-hit” MM. Finally, we suggest that a comprehensive profiling of the BCL2 pathway may identify biomarkers of sensitivity to BCL2 inhibitors in addition to the t(11;14)."

IO biomarker • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • BCL2L1 • BRAF • IRF4 • KRAS • NRAS • RB1 • TP53

MCL1 regulates cell death, tumor growth and chemosensitivity to sabutoclax in ovarian adenocarcinoma. (PubMed, Cell Tissue Res) - "Lastly, it was found that MCL1 knockdown significantly promoted ovarian carcinoma cell death and the sensitivity to sabutoclax. Thus, we concluded that MCL1 acted as a cancer facilitator in ovarian adenocarcinoma and it is also a suppressor of sabutoclax sensitivity."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Comparison of putative BH3 mimetics AT-101, HA14-1, sabutoclax and TW-37 with ABT-737 in platelets. (PubMed, Platelets) - "Since there are clear differences between the action of ABT-737 and the other putative BH3 mimetics investigated here, AT-101, HA14-1 and sabutoclax cannot be considered as acting as BH3 mimetics in platelets. Furthermore, the platelet death caused by these drugs is likely to be distinct from apoptosis."

Journal • BCL2 • BCL2L1

Hybrid Nanospheres to Overcome Hypoxia and Intrinsic Oxidative Resistance for Enhanced Photodynamic Therapy. (PubMed, ACS Nano) - "Once the hybrid nanospheres are uptaken by tumor cells, intracellular O2 concentration is observed to increase remarkably via Fenton reaction driven by Fe3+ while intracellular PDT resistance of the AIE PS was mitigated by sabutoclax. The design of the multifunctional hybrid nanospheres demonstrates a prospective nanoplatform for image-guided enhanced PDT of tumors."

Journal

Targeting STAT5 or STAT5-regulated pathways suppresses leukemogenesis of Ph+ acute lymphoblastic leukemia. (PubMed, Cancer Res) - "Treatment of Ph+ ALL cells, including samples from relapsed/refractory patients, with the PIM kinase inhibitor AZD1208 and/or the BCL2 family antagonist Sabutoclax markedly suppressed cell growth and leukemogenesis ex vivo and in mice. Treatment of Ph+ ALL cells, including samples from relapsed/refractory patients, with the PIM kinase inhibitor AZD1208 and/or the BCL-2 family antagonist Sabutoclax markedly suppressed cell growth and leukemogenesis ex vivo and in mice. Together, these studies indicate that targeting STAT5 or STAT5-regulated pathways may provide a new approach for therapy development in Ph+ ALL, especially the relapsed/TKI-resistant disease."

IO Biomarker • Journal

Sabutoclax, pan-active BCL-2 protein family antagonist, overcomes drug resistance and eliminates cancer stem cells in breast cancer. (PubMed, Cancer Lett) - "Our findings indicate that sabutoclax partially overcomes the drug resistance phenotype of breast cancer cells by reactivation of apoptosis, mediated by the inhibition of several anti-apoptotic BCL-2 family proteins, and eliminates CSCs by abolition of the IL-6/STAT3 pathway. This offers a strong rationale to explore the therapeutic strategy of using sabutoclax alone or in combination for chemotherapy-nonresponsive breast cancer patients."

Cancer stem cells • Journal