navitoclax (ABT 263) / AbbVie - LARVOL DELTA

DUAL THERAPEUTIC STRATEGY AGAINST LEPTOSPIRA-INDUCED RENAL PATHOLOGY: ANTIBIOTICS AND SENOLYTICS (ISN-WCN 2026) - "To assess the therapeutic potential of senolytic intervention, ABT-263 was administered following DAT, and its effects on senescent cell clearance and renal repair were examined using morphological, molecular, and biochemical analyses.Results EAT effectively eradicated Leptospira and prevented tubular damage, preserving renal function...A dual therapeutic strategy combining timely antibiotic administration to eradicate Leptospira with senolytic therapy to remove senescent cells, offers a promising approach to prevent CKD progression. This study highlights the importance of targeting both infection and host cellular responses in the comprehensive management of leptospirosis."

Acute Kidney Injury • Chronic Kidney Disease • Fibrosis • Immunology • Infectious Disease • Inflammation • Nephrology • Renal Disease • CDKN1A

Preliminary Safety and Efficacy of Navitoclax Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Patients With Myelofibrosis From the Multicenter, Open-Label, Phase 2 Study (REFINE). (PubMed, Hematol Oncol) - P2 | "These findings suggest navitoclax plus ruxolitinib has a tolerable safety profile and provides clinically meaningful improvements for JAKi-naïve patients with myelofibrosis. TRIAL REGISTRATION: NCT03222609."

IO biomarker • Journal • P2 data • B Cell Lymphoma • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Myelofibrosis • Non-Hodgkin’s Lymphoma • Oncology

Bst2-targeted senotherapy restores visual function by eliminating senescent retinal cells. (PubMed, Nat Commun) - "In vivo administration of ABT-263-loaded B-Z-PON in aged and senescence-induced retinal degeneration models resulted in the selective ablation of senescent cells, restoration of RPE function, and improved visual outcomes. Together, our study integrates senescence-specific marker discovery with precision nanomedicine, establishing a versatile platform for targeted senotherapy. These findings offer a promising therapeutic approach for retinal aging disorders, such as age-related macular degeneration."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • BST2

Addition of navitoclax to ruxolitinib for patients with myelofibrosis with progression or suboptimal response. (PubMed, Blood Neoplasia) - P2 | "NAV+RUX was tolerable and demonstrated early improvement in disease modification parameters in this difficult-to-treat population. This trial was registered at www.ClinicalTrials.gov as #NCT03222609."

Clinical • Journal • B Cell Lymphoma • Fibrosis • Hematological Disorders • Immunology • Lymphoma • Myelofibrosis • Oncology • Thrombocytopenia • BCL2

PRMT5 inhibition enhances therapeutic vulnerability to Bcl-xL/Bcl-2 inhibitors in glioblastoma (AACR 2026) - "We then evaluated the therapeutic potential of combining PRMT5 inhibition, using the CNS-penetrant PRMT5 inhibitor LLY-283, with navitoclax. Mitochondrial functional assays demonstrated a substantial decrease in ATP production along with elevated mitochondrial reactive oxygen species (ROS), implicating mitochondrial dysfunction in the enhanced apoptotic and DNA-damage responses observed under dual inhibition.In summary, our findings elucidate that PRMT5 inhibition creates a senescence-associated vulnerability in patient-derived glioblastoma cells, which can be effectively exploited through BCL-2/xL blockade. This combinatorial strategy offers a promising therapeutic avenue for overcoming the intrinsic resistance of glioblastoma."

IO biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • ANXA5 • BCL2 • BCL2L1 • MCL1

Senescent tumor-associated macrophages promote peritoneal metastatic niche formation in gastric cancer (AACR 2026) - "Pharmacologic clearance of senescent cells with the senolytic agent ABT263 markedly reduced peritoneal tumor formation, and macrophage-specific p16INK4a knockout further confirmed the essential role of senescent macrophages in metastatic niche formation. Complementarily, single-cell mass cytometry (CyTOF) of ascitic fluid from GC patients with peritoneal metastasis revealed a macrophage subset expressing p16 and SASP-associated factors. These findings uncover a previously unrecognized role of senescent macrophages in peritoneal metastatic niche formation and suggest that targeting senescent cells may represent a promising therapeutic strategy to limit peritoneal dissemination in GC."

Metastases • Gastric Cancer • Oncology • Peritoneal Cancer • Solid Tumor • CDH1 • CDKN2A • KRAS • TP53

Targeting BCL2 pathway to enhance immunogenicity in ALK+ NSCLC (AACR 2026) - "However, this has not been studied in the context of ALK+ NSCLC.We hypothesized that ALK-directed therapy in combination with BH3 mimetics would initiate ICD through the release of DAMPs and increase sensitivity to ALK TKIs. We evaluated the efficacy of ALK TKIs (Lorlatinib, Alectinib) alone and in combination with the BH3 mimetics navitoclax (BCL-2/BCL-xL inhibitor), venetoclax (BCL-2 inhibitor) and s63845 (MCL-1 inhibitor) to induce damage-associated molecular patterns (DAMPs) in ALK+ NSCLC cell lines. ALK+ cancer cell lines exhibited high expression of MCL-1 and BCL-xL proteins, indicating their dependency on BCL-2 family proteins for survival. ALK-directed therapy has the potential to induce immunogenic cell death (ICD) and elicit antitumor immune responses. Combining BH3 mimetics with ALK TKIs can be a promising therapeutic strategy to enhance anti-tumor immunity and overcome ALK TKI resistance in ALK+ NSCLC"

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BCL2L1 • CXCL10 • IFNB1

The mitochondrial antioxidant mitoquinone alters cancer cell death outcomes in response to therapy (AACR 2026) - "Therefore, to investigate how cell death outcomes might be adapted by changes to the cellular redox environment we used the mitochondrial antioxidant Mitoquinone (MitoQ) as a tool compound to dissect differences between apoptosis and ferroptosis outcomes in response to chemotherapeutic agents. Wild-type and BAX-/-BAK-/- HeLa (human cervical cancer) cells, as well as B16-F10 (metastatic murine melanoma) wild-type cells were treated with MitoQ (0.1-1 µM) alone or in combination with either an apoptosis-inducing cocktail of BH3 mimetics (1 µM ABT-263 + 1 µM S63845) or a ferroptosis-inducing cocktail (1 µM RSL3 + 1 µM Erastin2). These findings suggest that modulation of mitochondrial oxidative stress via MitoQ modulates cancer cell death outcomes, promoting apoptosis while suppressing ferroptosis at low doses. Further work is needed to elucidate the molecular mechanisms underlying these effects and their implications for modulating cancer cell death..."

Cervical Cancer • Melanoma • Oncology • Solid Tumor • ANXA5 • CASP3 • CASP7 • GPX4

PRMT5 inhibition alters cellular chromatin landscape and drives vulnerability to BH3 mimetics in mantle cell lymphoma (AACR 2026) - "Drug combination effects of PRT382 and BH3-mimetics (navitoclax, A852/A-1331852, PRT1419) were tested in MCL cell lines (n=5). Our study showed the broad synergistic potential of combining PRMT5i and BH3 mimetics both in vitro and in vivo. PRMT5i lead to epigenome-wide modulation of chromatin states with potential to create vulnerabilities to targeted agents."

IO biomarker • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2

Pharmacokinetics of a series of anticancer agents in immunodeficient female NOD scid gamma mice (AACR 2026) - "These PK data are critical for understanding the antitumor activities of agents studied by the PDXNet and will aid investigators in developing new approach methodologies for preclinical safety studies in preparation for human clinical trials."

PK/PD data • Preclinical • Oncology • BCL2 • CDK4 • FGFR • MAP2K1 • PARP1

Sequential senescence-escape cycles drive genomic heterogeneity and osimertinib resistance in EGFR-mutant NSCLC (AACR 2026) - "Although OsIS-derived lines retained sensitivity to cisplatin, they displayed heterogeneous responses to pemetrexed, while sensitivity to tubulin-interacting drugs and navitoclax was preserved. Despite these signatures, therapies directed at DNA repair or replication stress were uniformly ineffective, indicating that resistance was not driven by discrete genomic lesions but rather by age-associated mutational drift. These findings support a model in which OsIS functions as an evolutionary bottleneck whose escape promotes genomic heterogeneity and promotes resistance to EGFR inhibition."

Heterogeneity • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • TMB

JM (AACR 2026) - "Bcl-xL was targeted using the BH3 mimetic ABT-263 (navitoclax)... CDK12 inhibition activates an ISR-ATF4-Noxa signaling axis that lowers the apoptotic threshold and sensitizes GBM cells to Bcl-xL inhibition. Dual targeting of CDK12 and Bcl-xL represents a mechanistically defined strategy to overcome apoptosis resistance in GBM and may have broader therapeutic relevance across malignancies driven by Mcl-1-mediated survival."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • ATF4 • BCL2L1 • MCL1 • PMAIP1

Synergistic combinations of novel small molecule CtBP inhibitors with DR5 agonists or BH3-mimetic PROTACs targeting chemoresistant high grade serous ovarian carcinoma (AACR 2026) - "We demonstrate that NAS-2-134 exhibits target selective cytotoxicity in HGSOC cells via induction of caspase-8/DR5 dependent apoptosis in vitro and both NAS-2-134 and NAS-2-133 exhibit potent anti-HGSOC tumor activity in vivo; and 2) concerted targeting of CtBP and DR5 or Bcl-2/XL is synergistically cytotoxic in HGSOC cells and this strategy may lead to a future low toxicity precision therapy for chemoresistant HGSOC."

IO biomarker • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BCL2 • CASP8 • CTBP1

Synergy of BCL-2 and MEK/HDAC inhibition in IBC and non-IBC models: Potential for a first IBC specific therapy (AACR 2026) - "We then performed follow-up combination screens using Pimitespib (HSP90 inhibitor) and Navitoclax (BCL-2 inhibitor), the top hits within their respective classes, testing them against the same 1,200+ compound library to identify synergistic partners. This study shows for the first time a trend towards IBC-specific synergistic drug interactions. These findings suggest potential mechanistic differences in apoptotic regulation and may guide rational development of targeted combination therapies for IBC. Future studies will assess whether these in vitro synergy trends translate into subtype-specific therapeutic responses in vivo.AI disclosure: AI was used only for language editing; content was verified by the authors."

IO biomarker • B Cell Lymphoma • Breast Cancer • Inflammatory Breast Cancer • Lymphoma • Oncology • Solid Tumor • BCL2 • CDC37 • IRF4

Limited apoptotic response in RBM10 wild type/deficient EGFR-mutant lung cancer patient-derived models overcome by combined EGFR and BCL-2/BCL-xL inhibition (AACR 2026) - "RBM10 deficiency mediates intrinsic resistance to osimertinib by impairing mitochondrial apoptosis. Combined EGFR and BCL-2/BCL-xL inhibition fully restoresapoptotic signaling and provides superior and durable antitumor activity in RBM10-deficient EGFR-mutant lung cancer, even if not RBM10 mutant. These findings support the clinical actionability of cotargeting EGFR and BCL-2/BCL-xL in patients with EGFR-mutant/RBM10-deficient NSCLC.Keywords: EGFR, RBM10, NSCLC, osimertinib, ABT-263, BCL-xL, apoptosis, organoids, PDX"

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL2 • BCL2L1 • CASP3 • EGFR • EIF4EBP1 • RBM10

Preclinical investigation of the potential synergistic action of small molecule inhibitors in combination with chemotherapy in colon and liver cancer cells (ESMO-TAT 2026) - "MK2206, an AKT inhibitor, and Navitoclax, a Bcl-2 inhibitor can promote apoptotic signaling and potentially overcome resistance mechanisms. Overall, AKT inhibition sensitized liver and colon cancer cells to cisplatin, highlighting a promising combination strategy."

Combination therapy • IO biomarker • Preclinical • Colon Cancer • Liver Cancer • Oncology • Solid Tumor • ANXA5 • BCL2L1 • BIRC5

The synergistic effects of rhArg with Bcl-2 inhibitors and metformin cotreatment in multiple types of cancers (ESMO-TAT 2026) - "Background: The potentiation of Bcl-2 inhibitors (ABT263 and ABT199) and an antidiabetic drug metformin by cotreatment with recombinant human arginase (rhArg) was investigated in a panel of human cancer cell lines modeling pancreatic ductal carcinoma (PDAC), triple-negative breast cancer (TNBC), colorectal cancer (CRC) and glioblastoma (GBM). rhArg was combined with Bcl-2 inhibitors and metformin. ABT263, a clinical trial phase II drug candidate, and rhArg represent a promising broad-spectrum antitumor combination with clinical potential."

IO biomarker • Brain Cancer • Breast Cancer • Colorectal Cancer • Glioblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCNA2

Tacrolimus Induced Hypertension and Vascular Remodeling Includes Mechanisms of Cellular Senescence-The Protective Effect of Valsartan. (PubMed, Acta Physiol (Oxf)) - "These findings suggest that cellular senescence contributes to Tac-induced microvascular injury and hypertension and demonstrate the effectiveness of senolytic treatment for protection. Valsartan could reduce senescence indirectly by lowering blood pressure; a direct anti-senescence effect might also play a role in this context."

Journal • Cardiovascular • Hypertension • Immunology • Transplant Rejection • Transplantation

Targeting the Non-Homologous End-Joining Pathway Sensitizes MDM2-Amplified Liposarcoma to Doxorubicin by Enhancing p53-Mediated Senescence. (PubMed, Cancer Res) - "Three parallel genome-wide CRISPR-Cas9 knockout screens were conducted in DDLPS cells to sensitize to palbociclib (CDK4 inhibitor), nutlin-3a (MDM2 inhibitor) or doxorubicin...Genetic perturbation of TDP2 or pharmacological inhibition of DNA-PKcs using peposertib synergized with prolonged administration of low-dose doxorubicin to induce cell cycle arrest and senescence, and subsequent senolytic treatment with Bcl2 inhibitor navitoclax triggered senescent cells to undergo apoptosis...These findings provide a rationale for targeting the NHEJ pathway to enhance the efficacy of low-dose doxorubicin in DDLPS, highlighting a potential therapeutic strategy exploiting p53-mediated cell cycle arrest and senescence. Furthermore, this study provides evidence of maintained baseline p53 activity in MDM2-amplified DDLPS."

Journal • Liposarcoma • Oncology • Sarcoma • Solid Tumor • CCNE1 • CDK2 • CKS1B • E2F3 • MDM2 • PRKDC • XRCC4

Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming. (PubMed, NPJ Aging) - "Early "first-generation" senolytics, including navitoclax (ABT-263) and the dasatinib-quercetin (D + Q) combination, provided proof-of-concept that selective removal of SnCs can alleviate certain fibrotic, metabolic, and cardiovascular pathologies in preclinical studies. These approaches offer potentially more targeted and personalized therapeutic options but face significant challenges, including immunopathology, manufacturing complexity, off-target effects, and long-term safety concerns. The ongoing shift from broad inhibition to precision reprogramming represents a promising but preliminary step in the treatment of age-related diseases."

IO biomarker • Journal • Review • Cardiovascular • Fibrosis • Hematological Disorders • Inflammation • Oncology • Targeted Protein Degradation • Thrombocytopenia • Von Hippel-Lindau Syndrome • BCL2L1

Co-delivery nanoparticle targeting CAF for simultaneous activating T cell plus NKT cell attack in solid tumor. (PubMed, J Adv Res) - "Aim to develop a fibroblast-activated protein-α (FAP-α) responsive nanoparticle delivery system, (α-GC/NAV)-CPC, which encapsulates navitoclax (NAV) and alpha-galactosylceramide (α-GC)...Encouragingly, in in vivo models, (α-GC/NAV)-CPC treatment even led to 66.7% of mice achieving tumor eradication without recurrence. In further pulmonary metastasis challenge, mice treated with (α-GC/NAV)-CPC rarely displayed lung metastatic nodules."

Journal • Breast Cancer • Fibrosis • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • CAFs

Advancing Accurate Quantification of Protein-Ligand Interactions: Differential Scanning Calorimetry as a Precision Screening Tool Using BCL-2 as a Model System. (PubMed, ChemMedChem) - "Nine inhibitors (i.e., venetoclax, navitoclax; and seven previously prioritized BCL-2 hit inhibitors by our research group) are profiled across solvent systems, including neat DMSO, 10% DMSO, and a ternary matrix (S3: 10% DMSO, 90% sulfobutylether-β-cyclodextrin (SBE-β-CD) in saline). Comparisons with time-resolved fluorescence energy transfer (TR-FRET) analysis, in vitro assays, and MM/GBSA binding free energy results confirmed DSC's accuracy in detecting binding energetics. Collectively, these results position DSC as a robust, material-efficient tool for thermodynamic screening of BCL-2 ligands and other poorly soluble compounds, and as a practical complement to isothermal titration calorimetry when solubility or kinetic limitations prevail."

Journal • Oncology • BCL2

Evaluation of Drugs with Selective Inhibitors Targeting the Anti-Apoptotic Protein B-cell Lymphoma 2 (BCL-2) with Pro-Apoptotic and Antineoplastic Activities in Grade IV Glioblastoma. (PubMed, Turk Neurosurg) - "Venetoclax, navitoclax, and obatoclax represented significant advances in apoptosis-targeted therapy, with venetoclax emerging as the most clinically successful agent. However, resistance mechanisms and side effects were significant challenges, necessitating further preclinical and clinical studies to optimize the therapeutic potential of these agents."

Journal • Acute Myelogenous Leukemia • B Cell Lymphoma • Brain Cancer • Chronic Lymphocytic Leukemia • Glioblastoma • Hematological Disorders • Leukemia • Lymphoma • Oncology • Solid Tumor • Thrombocytopenia • BCL2 • BCL2L1 • MCL1

Differential responses to the combination of navitoclax and venetoclax with doxorubicin in murine models of triple negative breast cancer. (PubMed, Front Cell Dev Biol) - "These findings suggest that administration of venetoclax has the potential to enhance suppression of doxorubicin-exposed cancer cells, and that it may have potential as that of Bcl-xL-targeting agents. However, given the variable outcomes in the two triple-negative breast tumor cell lines, it becomes incumbent to identify the factors that confer susceptibility to Bcl- 2 targeting agents in anticipation of their potential utilization in the clinic for combination therapy in solid tumors."

Journal • Preclinical • Breast Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • Triple Negative Breast Cancer • ANXA5 • BCL2L1 • CDKN1A

REFINE: A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis (clinicaltrials.gov) - P2 | N=191 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed • Myelofibrosis