Our study uncovers a "C1orf35-driven" energy metabolism model in MM cells, providing new insights into the pathogenesis of MM and a potential novel target for the treatment of cancer cells with a high"C1orf35-driven" anabolic metabolism. Schematic diagram of C1orf35 simultaneously promotes glycolysis and OXPHOS.

These findings establish XZ739 as a promising therapeutic candidate for BCL-XL-dependent CCA, highlighting its translational potential for rational combination with chemotherapy to overcome resistance while mitigating hematologic toxicity.

Since ABT-263 is unlikely to be approved for the clinical treatment of solid tumors due to both on-target (thrombocytopenia) and off-target (neutropenia) toxicities, the few studies indicating improved radiosensitivity with ABT-199 (venetoclax) are intriguing, suggesting that targeting of Bcl-xL may not be a strict requirement for the combination strategy. Finally, it is worth noting that senolytic agents have the potential to protect normal tissue from radiation-induced damage, which may prove to be the most clinically relevant observation for this class of drugs.

APG-1252 enhanced the anticancer role of PTX in NSCLC cells by suppressing the ERK/MCL-1 pathway. This work provided the theoretical basis for the APG-1252 application.

The combination of rhArg and ABT263 enhanced apoptosis and cell cycle arrest, demonstrating a potential broad-spectrum antitumor strategy.

Morusin induces CRC cell senescence via the DNMT1/CDK2/p53 axis, and renders the cells vulnerable to senolytic agents. This study not only broadens the development and utilization of morusin but also provides a novel sequential therapeutic strategy for combating CRC.

Pathway and perturbation analyses suggested that NCI-LYM-1 harbored a strong dependency on apoptotic pathways, which was confirmed by in vitro organoid testing with the BCL-2/BCL-xL inhibitor navitoclax (IC 50 : 0.27 µM) and the MCL-1 inhibitor AZD-5991 (IC 50 : 0.060 µM). Overall, NCI-LYM-1 recapitulates the clinical aggressiveness and heterogeneity of AVPC, providing a tractable platform to identify novel precision therapies.

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with hypomethylating agents (HMAs) has improved treatment outcomes for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy and is increasingly used in the relapsed/refractory setting. Ex vivo treatment with the combination of navitoclax and SMAC mimetics further enhanced the eradication of VEN-HMA refractory blasts, although toxicity was also observed in healthy CD34+ cells. In conclusion, our integrative analysis identifies molecular signatures associated with primary VEN-HMA resistance and highlights BCL-2/BCL-XL inhibition and SMAC mimetics as therapeutic strategies to target resistance.

Brain irradiation induces liver proliferation, increased GFAP levels, and elevated ALT and AST activity, via mechanisms likely independent of senescence. Future investigation of blood GFAP levels is needed to determine whether the enhanced hepatic GFAP levels originate from the brain.

Using an in vitro co-culture system to assess CD8+ T cell killing of tumour cells, we identified compounds that inhibit Bcl-2 and Bcl-xl as agents that can induce tumour cell death without impacting the differentiation or function of anti-tumour T cells. Accordingly, in vivo treatment of mice bearing solid tumours with a combination of the Bcl-2/Bcl-xl inhibitor AZD0466 and anti-PD-L1 immunotherapy resulted in enhanced anti-tumour effects and improved survival compared to equivalent monotherapies.

Drug sensitivity analysis indicated that H-R patients were more sensitive to Staurosporine and Sabutoclax, whereas L-R patients were more sensitive to dihydrorotenone and osimertinib. RT-qPCR validated differential mRNA expression between KIRC and normal cells. This six-LRPMR-based prognostic model provides valuable insights for prognosis assessment and personalized treatment selection in KIRC.