P1, N=159, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

Additionally, the ability of phenformin to potentiate the antitumor effect of resveratrol and vistusertib was assessed...Our findings demonstrate that phenformin decreases the proliferation of various cancer cell lines in a dose-dependent manner and may have an ability to increase the autophagic flux in cervical cancer cells. Our findings demonstrate that phenformin decreases the proliferation of various cancer cell lines in a dose-dependent manner potentially by inducing apoptosis.

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Feb 2027 | Trial primary completion date: Jun 2026 --> Feb 2027

Patients in the high‑risk group showed improved responses to lapatinib, BI‑2536, OSI‑027, and SB505124, whereas those in the low‑risk subgroup had better sensitivity to axitinib, epirubicin, fulvestrant, and olaparib. Additionally, CD24 overexpression in BC cell lines promoted proliferation and migration, and inhibited apoptosis. These findings contribute to personalized treatment strategies and help elucidate the tumor microenvironment characteristics of BC patients.

Our findings identify vistusertib as a promising candidate for MASH, capable of mitigating disease progression and preventing MASH-to-HCC transition, highlighting its potential in managing metabolic liver disorders.

Compound 5 demonstrates distinct biological effects compared to torkinib and represents a promising candidate for further development as an mTOR inhibitor targeting both cancer and senescent cells.

Human and murine models resistant to combined belvarafenib and cobimetinib exhibited elevated levels of ATF4 and MTHFD2 and were sensitive to sapanisertib. This study provides promising treatment opportunities for patients with non-BRAF-mutant melanomas, or those who relapse following belvarafenib and cobimetinib combination therapy.

Ex vivo drug testing revealed a striking response: the mTOR inhibitor Sapanisertib induced extensive tumor necrosis and was associated with near-complete depletion of ALDH1A1+ and NTN4+ states, accompanied by strong stress/apoptosis signatures and reduced endothelial cells. In an additional retrospective cohort of 12 SDSC, ALDH1A1 was present in all cases with heterogeneous spatial patterns and higher levels in recurrences. Mesothelin was expressed in the index case and a subset of tumors, supporting mesothelin-directed therapeutic strategies.

P1/2, N=32, Recruiting, Faeth Therapeutics

The combined effects of two inhibitors, Torin 1, acting on mTOR, a key regulator of autophagy, and H-151, inhibiting STING, a key regulator of inflammation, on the autophagolysosomal system, have been studied in a primary culture of peripheral blood macrophages from healthy donors and the SH-SY5Y neuroblastoma cell line. Combined use of these drugs resulted in a decrease in the levels of lysosphingolipids, triggering alpha-synuclein oligomerization, as well as a decrease in the levels of monomeric and neurotoxic phosphorylated (Ser129) alpha-synuclein and an increase in tyrosine hydroxylase. These results open new prospects for the use of combination therapy with these proposed drugs in the treatment of both diseases associated with lysosomal dysfunction and neurodegenerative pathologies.

P1, N=99, Completed, AstraZeneca | Active, not recruiting --> Completed

P1, N=159, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026