ABT-737 / AbbVie - LARVOL DELTA

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

TPGS nanoparticles co-loaded with ABT-737 and R848 for breast cancer therapy. (PubMed, Biomed Pharmacother) - "This study demonstrated that TPGS NPs loaded with ABT-737 and R848 have superior combination tumor therapeutic effects, and the co-loaded preparation is conducive to anti-tumor efficacy. The TPGS/ABT+R848 NPs could be a promising platform against breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • BCL2

Coumarin-based Aldo-Keto Reductase Family 1C (AKR1C) 2 and 3 Inhibitors. (PubMed, ChemMedChem) - "Pan-AKR1C inhibition also did not potentiate the in vitro cytotoxicity of ABT-737, daunorubicin or dexamethasone, in two patient-derived T-cell ALL and pre-B-cell ALL cell lines.  In contrast, a highly selective AKR1C3 inhibitor, compound K90, enhanced the cytotoxicity of both ABT-737 and daunorubicin in the T-cell ALL cell line model. Thus, the inhibitory profile of the AKR1C family inhibitor required to effect enhancement of chemotherapeutic cytotoxicity may be chemotherapeutic agent-specific in leukemia."

Journal • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Oncology • Prostate Cancer • Solid Tumor • AKR1C2

Topical application of a BCL-2 inhibitor ameliorates imiquimod-induced psoriasiform dermatitis by eliminating senescent cells. (PubMed, J Dermatol Sci) - "We revealed the roles of senescent CD4+ T cells in developing psoriasis and highlighted the therapeutic potential of topical ABT-737 gel in treating psoriasis through the elimination of senescent cells, modulation of the TCR αβ repertoire, and regulation of the TET2-Th17 cell pathway."

IO biomarker • Journal • Dermatitis • Dermatology • Immunology • Lymphoma • Oncology • Psoriasis • CD4 • CDKN1A • CDKN2A • TET2

Melatonin Enhances the Effect of ABT-737 in Acute Monocytic Leukemia THP-1 Cells (PubMed, Mol Biol (Mosk)) - "Activation of CHOP stimulated autophagy and led to a decrease in the synthesis of chaperones BIP and PDI. It is assumed that melatonin can enhance the effect of other chemotherapeutic agents and can be used in the treatment of tumors."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BAX • MAP1LC3A

Targeting SERCA2 calcium pumps sensitizes chemoresistant ovarian carcinoma cells and patient-derived tumor organoids to the BH3-mimetic ABT-737 (EACR 2024) - "Introduction Ovarian cancer has a poor clinical prognosis due to innate or acquired chemoresistance following carboplatin/paclitaxel treatment...Therefore, we evaluated the interest of SERCA2 pumps inhibition to sensitize chemoresistant ovarian cancer cells to ABT-737, a BH3-mimetic that targets Bcl-xL.Material and Methods The platinum-resistant cell line, OAW42-R, was treated with anti-SERCA2 strategies (siRNA or thapsigargin), in combination with ABT-737...The use of PDTO supported the results obtained in 2D culture and improved their relevance. As it turns out, compounds enabling the induction of ER stress are currently in clinical trials in various cancers, consolidating the therapeutic interest of our study."

Clinical • IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • ATF4 • BCL2 • BCL2L1 • HRD • MCL1

Alterations in apoptosis and autophagy/ER-phagy signaling pathways contribute to the pathogenesis of immune thrombocytopenia (ISTH 2024) - "We observed a significant upregulation of CLU,GRP78,GRP94,CASPASE-3,-8 and BAX in MEG-01 cells treated with ITP plasma compared to healthy plasma controls (p < 0.05). The increased mRNA expression of these markers could be reversed upon treatment with either Z-VAD-FMK or Rapamycin. mRNA levels of all investigated markers were significantly increased upon ABT737 and ITP plasma treatment compared to healthy controls."

Hematological Disorders • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • CASP3 • CASP8 • CLU • HSPA5 • LAMP1

Senolysis of gemcitabine-induced senescent human pancreatic cancer cells. (PubMed, Cancer Rep (Hoboken)) - "Together, our results indicate that sequential treatment with GEM and senolytic drugs effectively kill human pancreatic cancer cells."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BCL2L1 • CXCL8 • IL6

Identification of senescent, TREM2-expressing microglia in aging and Alzheimer's disease model mouse brain. (PubMed, Nat Neurosci) - "Treating 5×FAD mice with the senolytic BCL2 family inhibitor ABT-737 reduced senescent microglia, but not the DAM population, and this was accompanied by improved cognition and reduced brain inflammation. Our results suggest a dual and opposite involvement of TREM2 in microglial states, which must be considered when contemplating TREM2 as a therapeutic target in AD."

Journal • Preclinical • Alzheimer's Disease • Amyloidosis • CNS Disorders • Dementia • Inflammation • TREM2

Isatin analogs potentiate the cytotoxicity of venetoclax in acute myeloid leukemia cells (AACR 2024) - "ISA also showed significant synergetic cytotoxicity in combination with ABT-737, a BH3 mimetic inhibitor of Bcl-xL, Bcl-2, and Bcl-w. Furthermore, our aim will be to demonstrate activity in primary patient cells along with preclinical efficacy in AML animal models. To summarize, in vitro findings showed synergetic cooperation between ISA and VEN in combination for effective induction of apoptosis and anti-leukemic activity in AML cells that are sensitive and resistant to VEN."

IO biomarker • Acute Myelogenous Leukemia • Leukemia • Lymphoma • Oncology • ANXA5 • BCL2L1 • BCL2L2