sirolimus

P2, N=28, Recruiting, University Hospital, Lille | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

Importantly, multiomics analyses reveal a unique mechanism of action: APT NPs induce the upregulation of the stress-responsive gene DNA damage-inducible transcript 4 (DDIT4), which inhibits the mammalian target of the rapamycin complex 1 (mTORC1) signaling pathway...In vivo, the MCF-7 tumor-bearing mouse model confirms potent antitumor efficacy without significant side effects. This work not only introduces a hypoxia-insensitive PDT agent but also provides novel insights into the mechanistic interaction between transcriptional and metabolic regulation in PDT, highlighting the potential of AIE-active materials for cancer therapy.

P1/2, N=35, Recruiting, Prevail Therapeutics | Trial primary completion date: Apr 2030 --> Apr 2031 | Trial completion date: Apr 2030 --> Apr 2031

P2/3, N=60, Active, not recruiting, University of Chicago | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=53, Recruiting, City of Hope Medical Center | Active, not recruiting --> Recruiting | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026

We discovered that BEX2 promotes autophagic flux via PI3K/AKT/mTOR signaling. BEX2 interacts with PIK3CA and impairs PIK3CA and p85 interaction, which hinders activation of PI3K/AKT/mTOR signaling and promotes autophagy induction.

The mechanistic target of rapamycin complex 2 (mTORC2) signaling pathway, which regulates cell growth and migration, exhibits oncogenic function in colorectal cancer (CRC)...In immunodeficient mice CRC xenografts, SLAP depletion enhanced mTORC2 activity and sensitized CRC cells to mTOR catalytic inhibitors. Together, our findings reveal a previously unrecognized SLAP-UBE3C-mLST8 axis that regulates mTORC2 integrity and suggest a potential therapeutic avenue for targeting mTORC2 in CRC.

THBS3-high breast cancer patients exhibited resistance to Dinaciclib, Daporinad, and Rapamycin. THBS3 may promote breast cancer progression through immune regulation, ECM remodeling, and drug resistance mechanisms, suggesting its potential as a therapeutic target. These findings support enhanced breast cancer screening in IBD patients.

We integrate data on epidermal growth factor receptor inhibitors, phosphoinositide-3-kinase inhibitors, taxanes such as docetaxel, fluoropyrimidines such as capecitabine, immune checkpoint inhibitors, BRAF and MEK inhibitors, mechanistic target of rapamycin inhibitors, Bruton tyrosine kinase inhibitors and chimeric antigen receptor T-cell therapy. We highlight the vulnerability of older adults, in whom age-related skin changes, comorbidities and polypharmacy amplify the impact of these events while evidence from dedicated prospective studies remains scarce. The review synthesizes practical, mechanism-oriented strategies for prevention and stepwise management, from basic skin care and photoprotection to targeted use of antibiotics, corticosteroids and treatment modification, with the goal of supporting timely recognition of cutaneous toxicity and multidisciplinary care that preserves both quality of life and the anticancer efficacy of therapy.

This broad, multi-pathway modulation mirrors the phenotype produced by metformin and rapamycin, yet occurred with no detectable cytotoxicity, paralleling metformin and rapamycin with negligible cytotoxicity. Although prospective clinical outcomes are still lacking, the pleiotropic mechanism profile positions C15:0 as a potentially unique nutraceutical or adjunct therapeutic candidate. Further research is warranted to confirm its clinical impacts, optimize dosing, and clarify long-term safety as an essential fatty acid supporting metabolic and immune homeostasis.

P2, N=57, Completed, Sidney Kimmel Cancer Center at Thomas Jefferson University | Active, not recruiting --> Completed