B-cell lymphoma 2

Overview

B-cell lymphoma 2 (BCL2) is a critical anti-apoptotic protein that plays a significant role in regulating cell death and survival. It is part of the Bcl-2 family of proteins, which are integral to the intrinsic pathway of apoptosis, a process essential for maintaining cellular homeostasis and tissue integrity. BCL2 functions by inhibiting the activation of pro-apoptotic factors, thereby preventing apoptosis in response to various cellular stressors. Its overexpression is frequently associated with several malignancies, including chronic lymphocytic leukemia and various solid tumors, making it a significant target for cancer therapies, particularly in the context of Targeted therapies like the venetoclax.

Focus of Latest Publications

Recent publications have continued to position B-cell lymphoma 2 (BCL2) as a central anti-apoptotic target across diverse cancer and disease models. Several studies evaluated BCL2 in combination with other pathway inhibitors or as part of multi-target therapeutic strategies. In acute myeloid leukemia, BCL2 inhibition was examined alongside PI3Kδ blockade, gemtuzumab ozogamicin, and venetoclax-based combinations, with reports of enhanced apoptosis, improved cytotoxicity, or synergistic effects in selected cell lines. In myelofibrosis, navitoclax, a BCL-XL/BCL-2 inhibitor, was combined with ruxolitinib and showed clinically meaningful activity in a phase 2 cohort. In castration-resistant prostate cancer, single-cell imaging, preclinical models, and a phase Ib trial supported BCL2 as a shared vulnerability, with venetoclax plus enzalutamide reducing circulating tumor cells in responding patients. A review on lymphoma therapies also highlighted BCL2-pathway targeting as a major component of the current precision-medicine landscape.

Other studies focused on natural products, engineered biomolecules, or computational screening approaches that implicated BCL2 in apoptosis regulation. Tetrahydroberberine was reported to bind and stabilize the bcl-2 promoter G-quadruplex, suppressing nasopharyngeal carcinoma cell proliferation and activating mitochondrial apoptosis through the Bax/bcl-2/caspase-3 axis. Nobiletin was described as a natural BH3 mimetic that downregulated BCL-2 and MCL-1 in non-small cell lung cancer cells, while also disrupting the Beclin-1/BCL-2 complex. berberine chloride, garlic-derived organosulfur compounds, and a nutraceutical polyherbal formulation were each assessed by docking or network pharmacology and were predicted to interact with BCL2 among other cancer-related targets. In hepatocellular carcinoma, a sophocarpine-derived compound was designed as a putative dual Bcl-2/Mcl-1 inhibitor and induced apoptosis with downregulation of both proteins. Similarly, an SN-38-nitrogen mustard conjugate reduced Bcl-2 protein levels and activated caspase-3 in tumor models.

BCL2 was also studied outside oncology in contexts where apoptosis, inflammation, or tissue injury were relevant. In a rat model of chronic stress-induced testicular damage, Ashwagandha increased Bcl-2 immunoreactivity and improved the Bax/Bcl-2 ratio. In ischemic stroke and cerebral ischemia-reperfusion injury models, poliumoside and eupalinolide B were reported to regulate Bcl-2 alongside oxidative stress and mitochondrial pathways. In diabetic neuroinflammation, FuBIG upregulated Bcl-2 while reducing Bax and caspase-3. In calcific aortic valve disease, engineered exosomes overexpressing bcl2 reduced apoptosis in cardiomyocytes and valve interstitial cells. In colorectal cancer, exosomal miR-21-5p was shown to suppress HRK, thereby relieving inhibition of Bcl-2 and promoting malignant progression. Across these studies, BCL2 repeatedly emerged as a marker and mediator of cell survival, with recent work emphasizing its value as a therapeutic target and as a node within broader apoptosis- and mitochondria-related signaling networks.

Key Publications

• NEWJul A network pharmacology-based approach and molecular docking study to explore the therapeutic potential of a nutraceutical formula (Vernolac) in the treatment of cancer. (PloS one, 2026, PMID 42384725): "Protein-protein interaction analysis using STRING and Cytoscape revealed fourteen key hub nodes, including AKT1, BCL2, CASP3, CTNNB1, EGFR, ESR1, GAPDH, HSP90AA1, HSP90AB1, IL6, JUN, SRC, STAT3, and TNF."
• NEWJun Clomipramine potentiates sorafenib efficacy in experimental hepatocellular carcinoma by targeting lysosomal sequestration and modulating the cathepsin B/Bcl-2/Beclin-1 axis. (Molecular biology reports, 2026, PMID 42377685): "...modulating the cathepsin B/Bcl-2/Beclin-1 axis."
• NEWJun A pilot single-case longitudinal multi-omics of canine oral melanoma characterizes endogenous mutation patterns and radiotherapy-associated responses. (Gene, 2026, PMID 42342053): "WGS of pre-treatment tumor tissue revealed a predominance of endogenous mutational processes, with frequent mutations in cancer-associated genes such as NTRK3, EGFR, and ADAM17, and structural variants affecting oncogenes like MDM2 and BCL2."
• NEWJun PI3Kδ inhibitor YY‑20394 is effective alone or in combination with Bcl‑2 inhibitor ABT199 in acute myeloid leukemia cells. (Oncology reports, 2026, PMID 42318952): "ABT199 (venetoclax) as a monotherapy shows limited effects in acute myeloid leukemia (AML), underscoring the need for novel combinatorial therapeutic strategies."
• NEWJun Protective effects of Withania somnifera (Ashwagandha) against chronic unpredictable mild stress-induced testicular damage in adolescent rats. (Journal of molecular histology, 2026, PMID 42315798): "Immunohistochemically, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), marker of proliferation Ki-67 (Ki67), and Sirtuin 6 (SIRT6) antibodies were evaluated."
• NEWJun Reverse engineering of BNIP3 identifies a mitochondrial protective peptide. (Nature communications, 2026, PMID 42309990): "...that directly activate BCL-2 executioner proteins, triggering mitochondrial cell death."
• NEWJun Bisphenol A exacerbates diabetic foot ulcers through disruption of immune microenvironment and repair processes: a multi-omics analysis of environmental exposure mechanisms. (Drug and chemical toxicology, 2026, PMID 42298305): "Three core targets were identified through network analysis: BCL2, EGFR, and MMP9."
• NEWJun Design, Synthesis, and Evaluation of Antitumor Activity of Novel Phenylahistin Derivatives with Double F-Substitution via Dual Inhibition of Microtubule and P53/BCL-2/BAX Signaling Pathways. (Journal of medicinal chemistry, 2026, PMID 42273719): "Further studies demonstrated that compound 45 not only disrupted the microtubule network and induced G2/M phase arrest but also enhanced p53 protein expression, thereby inhibiting the function of the antiapoptotic BCL-2 protein."
• Jun Combining bioinformatics and machine learning to analyze and validate sepsis-related cell senescence genes and potential drugs. (Renal failure, 2026, PMID 42219284): "This study identified eight differentially expressed senescence-related genes, including TXN, CDKN1C, UTP6, BCL11B, SMAD3, ITPKB, PRPF19, and BCL2, through bioinformatics analysis and machine learning."
• Jan Ethanolic extract of Otostegia fruticosa induces ROS-dependent apoptosis and reduces migration of MDA-MB-231 cells in vitro. (PloS one, 2026, PMID 42189838): "Altogether, this study demonstrates that Otostegia fruticosa induces apoptosis and inhibits metastasis in MDA-MB-231 cells by regulating caspase-3, 8, and 9, Bcl2, Bax, and Bid."