ABT-737 / AbbVie - LARVOL DELTA

Role of Bcl-2 Family Anti-apoptosis Inhibition in Overcoming Therapeutic Resistance in Prostate Cancer: A Systematic Review. (PubMed, Crit Rev Oncol Hematol) - "This systematic review demonstrates that inhibition of Bcl-2 family anti-apoptotic proteins can potentiate the efficacy of standard treatments for prostate cancer. These findings provide a compelling rationale for further research into targeted combination therapies to overcome therapeutic resistance in PCa."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BCL2 • BCL2L1

Prognostic significance of angiogenesis-associated molecules and Immunologic characteristic in elderly patients with acute myeloid leukemia. (PubMed, Ann Hematol) - "We have constructed an angiogenesis-related gene prognostic signature that enriches the prognostic assessment system for AML and provides novel therapeutic directions for this disease."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • EGLN1 • FKBP5 • FOXP1

Single-cell and spatial transcriptomics map senescent vascular cells in arterial remodeling during atherosclerosis in mice. (PubMed, Nat Aging) - "Using the SenMayo and CellAge gene sets, we identified four clusters of vascular smooth muscle cells (VSMCs), fibroblasts and T cells enriched in features of senescence, which were reduced upon treatment with the senolytic agent ABT-737...We validated the enrichment of these mRNAs in senescence by using spatial transcriptomics in a second mouse model of atherosclerosis and senolysis (Ldlr-/-; p16-3MR), as well as by analyzing in vitro models of human VSMC senescence. Our results uncover a vascular-specific transcriptomic signature of senescence that may be exploited for tracking and treating age-related vascular diseases."

Journal • Preclinical • Atherosclerosis • Cardiovascular • PCSK9 • SPP1 • TNFRSF11B

Bim and Mcl-1 Coordinate NVP-BEZ235-induced Renal Cell Carcinoma Cell Apoptosis. (PubMed, Arch Biochem Biophys) - "Bcl-2 inhibitor ABT-737 and Mcl-1 inhibitor AZD5991 predisposed NVP-BEZ235-treated cells to transform into the apoptotic phenotype. PI3K inhibitor LY294002 and Stat3 inhibitor AG490 duplicated the sensitized actions towards NVP-BEZ235...Data of in vivo tumor-bearing studies further revealed a better anti-tumor potential in the combination treatment of NVP-BEZ235 and MEK/ERK inhibitors without obvious toxicity. Our findings suggest that the feedback activation of pro-survival machinery is likely to be the main cause of cancer cells being refractory to NVP-BEZ235, and a combination treatment is a feasible strategy to sensitize cancer cell responses."

IO biomarker • Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Targeted Protein Degradation • BCL2L11 • MCL1

Integrated single-cell and bulk RNA dequencing to identify and validate prognostic genes related to T Cell senescence in acute myeloid leukemia. (PubMed, Front Bioinform) - "Prognostic genes showed strong binding activity to target drugs (IGF1R and ABT737)...CALR, CDK6, HOXA9, and PARP1 predicted disease progression and prognosis in patients with AML. Based on these, we developed and validated a new AML risk model with great potential for predicting patients' prognosis and survival."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CALR • CDK6 • HOXA9 • PARP1

Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1. (PubMed, Aging Cell) - "A senolytic by ABT-737 treatment alleviated the production of senescence-associated secretory phenotypes, the accumulation of senescent microglia, and the microglial hyperphagocytosis of excitatory synapses following LPS exposures. This treatment also restored reduced excitatory synaptic transmission, impaired long-term potentiation, and cognitive function in the model. These results indicate that reducing senescent microglia may potentially serve as a therapeutic approach to prevent neuroinflammation-related cognitive dysfunction."

Journal • CNS Disorders • Cognitive Disorders • Inflammation • CDKN2A

Proffered Paper: Targeting senescent macrophages inhibits metastatic dissemination in adrenocortical cancer (EACR 2025) - "These findings indicate that senescent immunosuppressive macrophages play a key role in metastatic dissemination in ACC. Their targeted clearance using senolytic therapy presents a promising therapeutic strategy for combating metastatic progression in this aggressive malignancy."

Metastases • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CDKN1B • PTPRC • ZNRF3

Overcoming Gemcitabine Resistance in MDA-MB-231 Cells: A Synergistic Approach Using ABT-737 and NVP-BEZ235 Dual Inhibition of PI3K/mTOR (EACR 2025) - "Our results suggest that the combination of ABT-737 and NVP-BEZ235 is a promising therapeutic strategy for overcoming Gemcitabine resistance in TNBC. This combinational approach enhances apoptosis and inhibits cell proliferation and migration by targeting both the PI3K/mTOR pathway and Bcl-2 family proteins. Further studies are needed to assess the potential of this strategy for GEM-resistant TNBC."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3 • ER • HER-2 • MCL1

Targeting Cellular Senescence to Enhance Human Endometrial Stromal Cell Decidualization and Inhibit Their Migration. (PubMed, Biomolecules) - "Although non-flavonoids exhibited notable cytotoxicity, dasatinib, but neither ABT-737 nor navitoclax, enhanced decidualization. Furthermore, flavonoid-senolytics and dasatinib consistently eliminated senescent eSCs. These findings support future studies to assess the therapeutic potential of in vivo supplementation with flavonoid senolytics on eSC function using menstrual effluent."

Journal • Endometriosis • Gynecology • Infertility • Sexual Disorders • Women's Health • TP53

The role of Sine Oculis Homeobox Homolog 2 in colon Cancer: Insights into prognosis, immune regulation, and therapeutic implications. (PubMed, Biochem Biophys Res Commun) - "Additionally, ABT737 was found to sensitize tumor immunotherapy in the context of SIX2...It could reduce the infiltration of CD163+ tumor-associated macrophages but without significantly increasing the infiltration of CD8+ T cells. Our findings suggest that SIX2 is a potential key player in CC, offering insights into future research and the development of targeted therapies."

IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Inflammatory Arthritis • Oncology • Solid Tumor • CD163 • CD8 • TGFB1

Prognostic and immunological role of RHEBL1 in pan-cancer: a target for survival and immunotherapy. (PubMed, Discov Oncol) - "Pan-cancer samples suggested that high RHEBL1 expression facilitates TAM infiltration and is correlated with tumour immunosuppressive status (TCGA). High expression of RHEBL1 may benefit from the therapy of 5-FU, ABT737, Afuresertib, AGI-5198, AGI-6780, and Alisertib."

IO biomarker • Journal • Pan tumor • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • CD8 • RHEB

Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. (PubMed, J Integr Med) - "Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; Epub ahead of print."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Solid Tumor • Targeted Protein Degradation • PMAIP1

Anti-tumor Effects of Curcumin and ABT-737 in Combination Therapy for Glioblastoma in Vivo. (PubMed, Int J Mol Cell Med) - "In conclusion, curcumin has the ability to inhibit the cell proliferation and migration, and activate the intrinsic pathway of apoptosis. Moreover, it can enhance the sensitivity of glioblastoma cells to ABT-737 by suppressing the expression of Mcl-1."

IO biomarker • Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BCL2 • CASP3 • MCL1

Selective apoptosis of tumor-associated platelets boosts the anti-metastatic potency of PD-1 blockade therapy. (PubMed, Cell Rep Med) - "We here demonstrate that selectively inducing apoptosis in tumor-associated platelets (TAPs) using ABT-737-loaded nanoparticles (cyclic arginine-glycine-aspartate containing peptide-modified ABT-737-loaded nanoparticles [cRGD-NP@A]) enhances the anti-metastatic efficacy of the anti-PD-1 antibody (aPD-1)...Combined with aPD-1, cRGD-NP@A substantially augments immune activation and reduces TAP-derived immunosuppressive factors, notably transforming growth factor β1 (TGF-β1), consequently improving anti-metastatic outcomes across multiple metastasis-bearing animal models without observable adverse effects. Our study underscores the importance of depleting TAPs to enhance PD-1 blockade therapy, presenting a promising strategy to improve response rates and clinical outcomes for patients with metastatic cancer."

Journal • Oncology • Solid Tumor • CTCs • TGFB1

An in vitro pharmacogenomic approach reveals subtype-specific therapeutic vulnerabilities in atypical teratoid/rhabdoid tumors (AT/RT). (PubMed, Pharmacol Res) - "Subtype-dependent drug response profiles demonstrated sensitivity of AT/RT-SHH cell lines to B-cell lymphoma 2 (BCL2) and heat shock protein 90 (HSP90) inhibitors, and increased activity of microtubule inhibitors, kinesin spindle protein (KSP) inhibitors, and the eukaryotic translation initiation factor 4E (eIF4E) inhibitor briciclib in a subset of AT/RT-MYC cell lines. In summary, our in vitro pharmacogenomic approach revealed preclinical evidence of tumor type- and subtype-specific therapeutic vulnerabilities in AT/RT cell lines that may inform future in vivo and clinical evaluations of novel pharmacological strategies."

IO biomarker • Journal • Preclinical • B Cell Lymphoma • Brain Cancer • CNS Tumor • Embryonal Tumor • Glioma • Lymphoma • Malignant Glioma • Medulloblastoma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • BCL2 • CDC37 • EIF4E • HSP90AA1 • SMARCA4 • SMARCB1

Senolytic Targeting of Anti-Apoptotic Bcl Family Increases Cell Death in UV-Irradiated Senescent Melanocytes: Search for Senolytics. (PubMed, Exp Dermatol) - "The senolytic effects of the ABT drugs were associated with increased expression of cleaved caspase-3, which was hindered with a caspase inhibitor, Z-VAD. These findings indicate that ABT-737 and ABT-263 eliminate senescent melanocytes through caspase-mediated apoptosis, suggesting their future potential to address ageing skin."

Journal • CASP3 • CDKN1A • CDKN2A

Characterizing and Targeting of BCL-2 Family Members in Nasopharyngeal Carcinoma. (PubMed, Head Neck) - "Our study demonstrates the therapeutic potential of combining cisplatin and S63845, which warrants further investigation."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • BCL2 • BCL2L1 • MCL1

Enhancement of the Sensitivity of the Acute Lymphoblastic Leukemia Cells to ABT-737 by Formononetin. (PubMed, Int J Mol Cell Med) - "In summary, formononetin showed anti-carcinogenic activities in human ALL cells via suppression of cell growth and survival. Formononetin enhanced the apoptotic effect of ABT-737, with contribution by inhibition of the Mcl-1 expression."

IO biomarker • Journal • Acute Lymphocytic Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BAX • BCL2 • CASP3 • CDKN1A

Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells. (PubMed, PLoS One) - "In this study, we have shown the cytotoxicity of BDM alone and in combination with novel agents including the histone deacetylase (HDAC) inhibitor tucidinostat, the enhancer of zeste homolog 1/2 (EZH1/2) dual inhibitor valemetostat, and the Bcl2 family inhibitor ABT-737. Our present results suggest that the combination of tucidinostat and BDM could additively prolong the survival of patients with R/R progressive ATL. The efficacy and safety of this combination are thus worthy of investigation in clinical settings."

Combination therapy • Journal • Adult T-Cell Leukemia-Lymphoma • Alopecia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • EZH2

INVESTIGATION FOR A ROLE OF NON-APOPTOTIC CELL DEATH IN THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA (AASLD 2024) - " In Huh7 cells, ABT737 administration led to an increase in caspase-3/7 activity in the supernatant and Dfna5 fragmentation, which is reported to be essential for the induction of secondary necrosis...Deletion of Kupffer cells using clodronate liposomes completely suppressed Tnfa expression in Mcl-1 L-KO mice, suggesting that Kupffer cells engulfed non-apoptotic cells and secrete Tnfa... Non-apoptotic cell death is suggested to contribute to the progression of HCC."

Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • BCL2L1 • CASP3 • CASP7 • FASLG • GSDME • MCL1 • TNFA

Runx2 silencing sensitized human renal cell carcinoma cells to ABT-737 apoptosis. (PubMed, Arch Biochem Biophys) - "Since overexpression and prognostic roles of Runx2, activated Akt, Mcl-1, fibronectin, cyclin D1, and β-catenin have been revealed in RCC, it is important to explore the precise mechanisms underlying Runx2 oncogenic effects. Although the linking details between Runx2 and PI3K/Akt have yet to be identified, our findings suggest that Mcl-1 and fibronectin are downstream effectors of Runx2 via a regulatory axis of the PI3K/Akt and their promotion of cell growth, migration, and ABT-737 resistance in RCC cells."

IO biomarker • Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CCND1 • FN1 • MCL1 • RUNX2

Topical Administration of a BCL-2 Inhibitor Alleviates Cutaneous Lupus Erythematosus by Targeting Senescent Cells and Age-Associated B Cells (EADV 2024) - "These findings establish a strong theoretical basis, indicating that the senolytic ABT-737 gel delayed CLE disease progress through targeting senescent cell populations. Our study provides promising and robust preclinical evidence supporting the therapeutic potential of ABT-737 gel in the treatment of CLE."

Cutaneous Lupus Erythematosus • Dermatitis • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Oncology • CDKN1A

Topical administration of a BCL-2 inhibitor alleviates cutaneous lupus erythematosus. (PubMed, Int Immunopharmacol) - "These findings suggest that the senolytic ABT-737 gel delayed the progression of CLE by targeting senescent cell populations. In conclusion, our study provides promising preclinical evidence supporting the therapeutic potential of ABT-737 gel for CLE treatment."

Journal • Cutaneous Lupus Erythematosus • Dermatitis • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Oncology

Development of CD33-Targeted Dual Drug-Loaded Nanoparticles for the Treatment of Pediatric Acute Myeloid Leukemia. (PubMed, Biomacromolecules) - "Here, we investigated ABT-737 and Purvalanol A as a potential drug pairing for pediatric AML and described the development of CD33-targeted polymeric nanoparticles (NPs) to enable their simultaneous targeted codelivery. Moreover, conjugation to gemtuzumab resulted in improved NP binding and internalization in CD33-positive cells. Finally, CD33-targeted dual-loaded NPs showed enhanced cytotoxicity to CD33-positive AML cells via CD33-mediated targeted drug delivery."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD33

ABT‑737 increases cisplatin sensitivity through the ROS‑ASK1‑JNK MAPK signaling axis in human ovarian cancer cisplatin‑resistant A2780/DDP cells. (PubMed, Oncol Rep) - "Therefore, upregulation the ROS‑ASK1‑JNK signaling axis is a potentially novel molecular mechanism by which ABT‑737 can enhance cisplatin sensitivity of ovarian cancer cells. In addition, the present research can also provide new therapeutic strategies and new therapeutic targets for patients with cisplatin‑resistant ovarian cancer with high Bcl‑2/Bcl‑xL expression patterns."

Journal • Colorectal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • BCL2 • BCL2L1