PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

P3, N=440, Not yet recruiting, Shanghai Jiatan Pharmatech Co., Ltd

These results indicate that PI3Kγ contributes to cSCC development not by directly driving tumour cell proliferation but by shaping an immunosuppressive tumour microenvironment. Targeting PI3Kγ may therefore represent a promising immunotherapeutic strategy to enhance cytotoxic T-cell-mediated antitumour immunity in cSCC.

The interpretable DeepSurv model, integrating multimodal features, enables quantitative survival prediction and risk stratification in advanced NSCLC, facilitating personalized decision-making.

Patients with p16 (+) showed longer PFS and OS compared to p16 (-) patients. This suggests that p16 has prognostic and predictive values in HNSCC patients who are treated with MTAs or ICIs.

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.

Together, these structure-informed alleles show that discrete PI3K structural perturbations can differentially uncouple lifespan, growth, and developmental outcomes in vivo . By combining structural modeling with genome editing in a tractable aging model, this work establishes a framework for dissecting conserved signaling enzymes at single-residue resolution and uncovers unexpected organismal roles for PI3K structure in coordinating growth and longevity.

Persons who have a more pro-inflammatory lifestyle may have an increased recurrence risk (IRR 1.21, 95% CI 0.97-1.52), which was most pronounced for persons with MSS and KRAS or PIK3CA wildtype tumours (IRR 1.31, 95% CI 0.90-1.90 and IRR 1.30, 95% CI 0.98-1.71, respectively). Our results suggest that associations between the LIS and recurrence might differ based on molecular tumour characteristics.

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.

Methods We performed whole exome sequencing (WES), bulk RNAseq, multiplex immunofluorescence (mIF) and chromogenic immunohistochemistry (IHC) on tumor tissue and flow cytometry of the peripheral blood to study longitudinal changes following the combination of avelumab with utomilumab (a 4-1BB agonist) (arm A), PF-04518600 (an OX40 agonist) (arm B), utomilumab and PF-04518600 (arm C) and utomilumab and radiotherapy (arm D) in phase I/II study (NCT03217747). Conclusions Our findings, though limited, highlight genomic differences between histologic subsets and outcome as well as the need for combination strategies that drive the recruitment and/or priming of anti-tumor T cells and address low immune permissive tumor states in patients with advanced solid tumors. Clinical trial registration: This clinical trial was registered on clinicaltrials.gov NCT03217747.

P3, N=480, Recruiting, University of Campania Luigi Vanvitelli

P1/2, N=320, Recruiting, Pikavation Therapeutics, Inc. | Phase classification: P1 --> P1/2 | N=140 --> 320 | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Oct 2026 --> Apr 2027

These data provide an expanded understanding of the molecular underpinnings of EMCG-including the first description of a SMARCA4 frameshift variant in this entity-and demonstrate that while gastrointestinal marker immunoexpression is relatively common among endometrial carcinomas, strictly defined EMCG remains rare (<1%). As awareness of this entity grows, pathologists should take care not to over-interpret gastrointestinal marker expression as stand-alone evidence of an EMCG diagnosis.