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

P1, N=100, Recruiting, Newave Pharmaceutical Inc | Trial completion date: Oct 2025 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2026

ECE2, NFE2L3, PFKFB3, FADS2, and SEPT3 are associated with pyrimidine metabolism in TNBC. A risk model and nomogram were successfully constructed based on these genes, providing a theoretical basis for the treatment of TNBC patients. We confirm the model's validity in TNBC by validating SEPT3 (a key PyMRG) regulates TNBC cell proliferation, migration, and invasion.