Importantly, this synergistic interaction was tumor-specific and absent in non-malignant fibroblasts, indicating a favorable therapeutic window. Together, these findings highlight the mevalonate pathway as a targetable metabolic dependency in ES and demonstrate how physiologically grounded 3D models can uncover clinically actionable treatment strategies that remain hidden in traditional 2D systems.

Indeed, genetic inactivation of NOXA, which reinforces the pro-survival function of MCL-1 in cancer cells, only postpones death upon exposure to Taxol and BCL-xL antagonism with A1331852. Importantly, a comparative analysis of secretomes from NOXA-proficient and NOXA-deficient cancer cells treated with Taxol revealed variations in the production of inflammatory cytokines, including IL-1α, IL-1β, and IL-18. Thus, induction of apoptosis or a vacuole-associated and inflammatory cell death, in breast cancer cells by antimitotic treatment, relies on pore-forming protein GSDME expression but also on a fine balance within the BCL2 family network.

Lung mesenchymal stem cells (MSCs; platelet-derived growth factor receptor α+ CD31- CD45- CD326- cells) were isolated and differentiated into myofibroblasts by culturing them with 15% fetal bovine serum (FBS) for 6 d. In asthmatic lungs, α-SMA+ myofibroblasts showed increased Bcl-xL expression, which was unaffected by dexamethasone (DEX) treatment. However, co-treatment with the Bcl-xL inhibitor navitoclax significantly restored steroid sensitivity...These findings indicate that Bcl-xL-expressing myofibroblasts contribute to the development of glucocorticoid resistance in fibrotic lungs in severe asthma. Targeting Bcl-xL may provide a novel therapeutic strategy to restore steroid responsiveness in severe asthma.

Functionally, PRMT5 inhibition induces senescence in LKB1-deficient cells and confers vulnerability to navitoclax, synergistically blunting tumor growth in vivo. Collectively, we identify PRMT5 as an actionable therapeutic vulnerability in LKB1-deficient lung cancer, and propose LKB1 status/NNMT expression as potential biomarkers for PRMT5 inhibition. These findings may expand the clinical utility of PRMT5-targeted therapies beyond MTAP-deleted cancers.

P1/2, N=52, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Sep 2026 --> May 2026

Significantly, YTHDC1-depleted senescent cells displayed enhanced sensitivity to the senolytic agent, ABT-263. Collectively, these findings uncover a previously unrecognized epitranscriptomic-telomerase axis that dictates senescence escape, establishing YTHDC1 as a central node linking RNA modification to telomere maintenance, cellular senescence, and tumor progression.

P1, N=26, Not yet recruiting, Wake Forest University Health Sciences

Navitoclax added to venetoclax/decitabine is safe and tolerable with preliminary activity in patients with high-risk myeloid malignancies.

Sabutoclax treatment was associated with both decreased protein expression and reduced nuclear translocation of NFATc1. Future studies could focus on comprehensive evaluation of its pharmacokinetic properties, systemic toxicity, and therapeutic efficacy in more clinically relevant metastatic models to establish its potential application in breast cancer-induced osteolytic bone destruction.

P1, N=6, Completed, Thomas Jefferson University | Active, not recruiting --> Completed

Integrated PK/PD model simulations suggested that a flat starting dose of navitoclax 200 mg for baseline platelets > 150 × 109/L, and 100 mg for ≤ 150 × 109/L with ruxolitinib minimized thrombocytopenia risk while maintaining efficacy. Dose reductions of 25 mg for the 100 mg start and 50 mg (plus 25 mg if needed) for the 200 mg start optimized the benefit-risk balance.

P1, N=0, Withdrawn, M.D. Anderson Cancer Center | N=24 --> 0 | Trial completion date: Jun 2032 --> Apr 2026 | Initiation date: Aug 2026 --> Apr 2026 | Not yet recruiting --> Withdrawn | Trial primary completion date: Jun 2030 --> Apr 2026