BCL2L11 (BCL2 Like 11)

Moreover, BIM loss conferred broad resistance to chemotherapy and clinically relevant targeted agents. In contrast, treatment with bispecific T-cell engagers elicited robust cytotoxic responses regardless of BIM expression, underscoring the potential of immunotherapies to overcome TME-induced apoptotic resistance.

In summary, paclitaxel induces transcriptomic and proteomic signatures of the neuronal stress response, neuroinflammation, nociception, and disturbed metabolism. These may explain, in part, the clinical phenotype of sensory loss, hypersensitivity, and neuropathic pain frequently observed in patients suffering from CIPN, but constitute pharmacologically addressable targets.

Systematic elucidation of the complexity of the FoxO3a signaling network and its dual roles in breast cancer therapy may provide theoretical support for understanding tumor-drug resistance mechanisms and for developing precision therapeutic strategies targeting FoxO3a nodes. Future research should further clarify the functional differences among FoxO3a splice variants and FoxO family members, reveal the molecular basis of FoxO3a functional switching in the tumor microenvironment, and promote the clinical translation of biomarkers and targeted drugs.

Mechanistic investigations further identified E-cadherin (CDH1) as a key downstream effector, showing significant down-regulation following TMBIM1 knockdown. We therefore define a context-dependent tumor-suppressive mechanism for TMBIM1, wherein its loss in MSI-H cells promotes tumorigenesis via E-cadherin suppression and the consequent loss of epithelial integrity.

Finally, we propose a novel treatment strategy involving the synergistic inhibition of bladder cancer cell growth by combining TAK-901 with Afatinib. Our research strongly suggests that Aurora A and Aurora B are promising epigenetic therapeutic targets in bladder cancer. Furthermore, TAK-901 can function as a targeted kinase inhibitor and EGFR inhibitor for the treatment of bladder cancer by activating the FOXO signaling pathway, which induces apoptosis in bladder cancer cells.

The patient was initially treated with alectinib, but experienced rapid disease progression. After repeat genetic testing, therapy was switched to lorlatinib, which again resulted in early progression...To our knowledge, this is the first reported case of ivonescimab use in such a patient. This case offers a potential reference for the management of ALK fusion-positive lung adenocarcinoma resistant to ALK tyrosine kinase inhibitors (ALK-TKIs).

Pharmacological inhibition of Hsp70-Bim blocks mitophagy, leading to the differentiation of CML LSCs, loss of quiescence, and loss of LSC self-renewal potential. In the patient-derived xenograft (PDX) CML models, S1g-10 reduces the number of LSCs by more than 80% after two weeks of injection, without obvious toxicity on normal red blood cells.

This highlights the necessity of achieving an optimal hydrophobic-hydrophilic balance for effective Mcl-1:peptide interactions. The study connects thermodynamics and structures to clarify the mechanism of peptide recognition by Mcl-1, providing valuable insights for designing Bim variants with enhanced affinity.

A fragment-assisted screen then delivered a phenalene-dicarbonitrile chemotype, S1g-2, and optimized analogs that displace Bim with sub-micromolar potency, dismantle Hsp70-client hubs, and resensitize resistant xenografts to imatinib or tamoxifen without global proteostasis collapse. Future directions include covalent or macrocyclic wedges, degrader hybrids, and adaptive pulse-dose regimens guided by proximity-ligation assays. Collectively, chemical disarming of the Hsp70-Bim alliance exemplifies how precision targeting of chaperone PPIs can recalibrate apoptotic thresholds and unlock new therapeutic space in oncology.

These observations suggest that the AMPK signaling pathways activated by PARP-1-dependent ATP depletion limit parthanatos by blocking the Bim upregulation triggering Bim-mediated parthanatos. Thus, our results demonstrate a novel relationship between AMPK and parthanatos, which may provide insights into the physiological roles of parthanatos.

Triptolide exerts dual anti-glioma effects by inducing apoptosis and reshaping the tumor immune microenvironment. By shifting macrophages toward a pro-inflammatory M1 phenotype and activating apoptotic pathways, triptolide emerges as a promising candidate for glioma immunotherapy.

Small-molecule inhibitors such as ABT-737 and Navitoclax, kinase inhibitors targeting NF-κB (Nuclear Factor kappa-light-chain-enhancer of Activated B Cells) and JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) pathways, and natural compounds including fucoxanthin, peridinin, and thymoquinone have demonstrated the ability to overcome apoptosis resistance in preclinical models. Recent strategies combining MCL-1 inhibitors with antiretroviral therapy or immune checkpoint blockade further highlight the translational potential of targeting BCL-2 pathways. Collectively, the evidence positions the BCL-2 family as a critical determinant of deltaretroviral persistence and leukemogenesis, and as a promising therapeutic axis for the development of novel treatments for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and BLV-associated leukosis.