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

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.

Despite these developments, the clinical translation of multi-omics findings remains limited due to the lack of standardized analytical pipelines, insufficient multi-center validation, and the high cost and technical complexity of integrating multi-omics data into routine clinical workflows. Future research integrating artificial intelligence with multi-omics data holds promise for enhancing diagnostic accuracy and enabling more precise therapeutic decision-making in ESCC.

Despite some significantly different clinicopathological features, there is no solid evidence to support HER2-ultralow, HER2-low and HER2-null cancers as individual TNBC clinical-molecular entities. Particularly, assigning TNBC samples to the HER2-null, -ultralow and -low categories did not bring any additional prognostic value.

Our findings suggest that PD-L1 immunohistochemistry is effective for evaluating pleural fluid cytological specimens and that PD-L1 expression is significantly higher in lung adenocarcinoma patients with malignant pleural effusions associated with the KRAS, ALK and BRAF mutations.

Despite first-line carboplatin, nab-paclitaxel, and pembrolizumab followed by second-line carboplatin, pemetrexed, nivolumab, and ipilimumab, the disease progressed rapidly, and the patient died four months after diagnosis. This case illustrates that isolated PIK3CA-mutant NSCLC can be highly refractory to conventional chemoimmunotherapy, including regimens incorporating a cytotoxic T-lymphocyte-associated antigen 4 inhibitor. Further clinical investigation of PI3K-targeted therapies is warranted to establish effective treatment strategies for PIK3CA-mutant NSCLC.

Importantly, wet-lab evaluation of the FDA-approved drug confirmed its inhibitory activity, thereby supporting the computational predictions. Overall, our integrated in silico and experimental framework highlights promising PI3K-α inhibitors, underscoring the potential of applicability domain-based virtual screening and QSAR modelling for both drug discovery and repurposing.

Combining biomarker-driven immunotherapy and targeted approaches such as PD-1 blockade in MSI-H or EBV-positive tumors, HER2-directed therapy, and CLDN18.2 inhibition, has demonstrated a paradigm shift in the clinical management. This review highlights a pathologist-centered perspective on molecularly defined subgroups, actionable biomarkers, and evolving therapeutic paradigms in CRC and GEJ carcinoma, advancing precision oncology.

P1, N=90, Not yet recruiting, Cogent Biosciences, Inc.

This case underscores the broader phenotypic spectrum of LFS. With the growing use of CGP, LFS may be identified more frequently in East Asia, potentially revealing attenuated LFS missed by traditional diagnostic criteria.

Based on the findings, the patient opted for off-label therapy with alpelisib, an α-specific PI3K inhibitor that selectively targets p110α and has shown promising efficacy in breast cancer patients harboring the identical PIK3CA mutations. However, no clinical response was observed in the patient, and the lack of response may be associated with the specific nature of the PIK3CA mutation, and/or other unfavorable tumor biological factors that override any benefit from alpelisib.