Truqap (capivasertib)

P1/2, N=104, Recruiting, University of Chicago | Not yet recruiting --> Recruiting

P1, N=20, Completed, AstraZeneca | Recruiting --> Completed

Potential therapeutic agents (e.g. capivasertib, lenalidomide) were predicted, and lenalidomide may represent a feasible initial treatment option for PTCL, with an objective response rate (ORR) of 40.0% and a maximum survival duration exceeding 50 months. NET-RGs play crucial roles in diagnosis, prognosis, and TME regulation, and lenalidomide, a putative TNF-targeting agent, may represent a feasible initial treatment option in PTCL.

A sonic hedgehog (SHH)-MB model, including a Gorlin syndrome patient neuroepithelial stem cell line (NES) and its tumor derivative (tNES), was used to evaluate single and combined treatments of PI3K, AKT, FGFR, and CDK4/6 inhibitors (BYL719, AZD5363, JNJ-42756493, and PD-0332991, respectively). This study illustrates that single and combined administrations of PI3K, FGFR, CDK4/6, and AKT inhibitors in a NES/tNES model have dose-dependent and additive/synergistic anti-MB activity impacting tumor growth. Their effects on tNES cells were generally more pronounced than on NES; however, the difference in proliferative capacity between the cells should be considered.

P=N/A, N=48, Completed, AstraZeneca | Recruiting --> Completed

P2, N=108, Not yet recruiting, Maryam Lustberg

P2/3, N=272, Recruiting, Relay Therapeutics Inc.

P1, N=42, Recruiting, AstraZeneca AB

In Cap-R cells, the combination of Cap and WH23 significantly induced apoptosis, demonstrating a synergistic anticancer effect. These findings establish WH23 as a dual-acting compound targeting both androgen biosynthesis and AR signaling, with potential to overcome AKT inhibitor resistance in LAR TNBC.

Taken together, this study leverages LLM-guided discovery to delineate a novel ALKBH5/CHRM3/ZNF281 regulatory axis controlling ferroptotic susceptibility in PCa. Importantly, a synergistic therapeutic strategy was identified by combining RSL3 with AZD5363, providing novel therapeutic targets and directions for PCa treatment.

Drug-gene mapping revealed candidates spanning already in clinical trials for HNC (e.g. Afatinib, Cabozantinib, Dasatinib, Brigatinib, Lenvatinib, Capivasertib, Erdafitinib) and emerging or repurposing candidates (Amuvatinib, XL765 (Voxtalisib), Golotimod, Artenimol, Quercetin, and Acetylsalicylic Acid), offering opportunities for precision repurposing...These included targeted therapies such as Fostamatinib, Nintedanib, Brigatinib, Regorafenib, and Lenvatinib, as well as emerging compounds like Artenimol, Quercetin, and Acetylsalicylic Acid (Aspirin). Through a combination of genomic analysis, network expansion, and literature validation, the GARD pipeline offers a powerful way to accelerate personalized cancer treatments while reducing cost and development time.

The pan-AKT inhibitor, Capivasertib (AZD5363), suppressed some but not all tested PIK3CA -mutated cell lines and one PIK3CA -wt cell line (SiHa). Further research on targeted therapies will improve the prognosis of patients with cervical cancer. Identified 3 molecular subtypes of CC based on PIK3CA and YAP1 amplification status Cervical cell lines with PIK3CA mutation are suppressed by targeted inhibitors PI3K inhibitors Alpelisib/Inavolisib selectively block PIK3CA-mutant cells PIK3CA mutation is associated with higher expression of the checkpoint CD274/PD-L1 PI3K inhibitors cooperate with donor-derived T cells to kill cervical cells.