PIK3CA mutation

Using clinical samples, we show that the DNAe panel with analysis using DNAe's pipeline detects mutations comparably to the commercial Oncomine-Assay. This paves the way for development of the DNAe panel into a test for the LiDia-SEQ platform.

In survival analysis using the Cox proportional hazards model, the presence of PIK3CA mutations was identified as being potentially associated with adverse prognosis (hazard ratio: 2.73, 95% confidence interval: 1.15-6.49, and p = 0.023). To enhance the prognosis of gynecologic cases, earlier CGP testing to expand the opportunities for GMT and the proactive introduction of PIK3CA-related clinical trials might be crucial.

In addition, pathogenic germline variants in MITF, NTRK1, and BAP1 were identified in three patients; notably, the NTRK1 germline variant was accompanied by an independent somatic mutation in the same gene. Overall, these findings support liquid biopsy as a valuable approach for molecular profiling of CUP and highlight the critical importance of paired ccfDNA/gDNA analysis, including CHIP assessment, to accurately distinguish somatic, germline, and hematopoiesis-related variants.

ctDNA represents a transformative tool in CC care, enabling real-time, tumor-specific insights with broad diagnostic and prognostic implications. Future efforts should focus on prospective validation, integration with imaging and artificial intelligence, and development of cost-effective ctHPV DNA screening panels, particularly for underserved populations.

CDX2 was detected exclusively in the morular structures. The somatic APC p.(Thr621Leufs*9) oncogenic variant and the somatic TERT promoter - 124 (C228T) oncogenic variant were found, in line with the tumor type and tumor grade respectively; but, for the first time, EWSR1 gene rearrangement was also detected, expanding the molecular spectrum of this uncommon entity.

A 62-year-old man with metastatic PSA underwent splenectomy followed by first-line paclitaxel, achieving stable disease for 7 months...Sequential treatment with liposomal doxorubicin, eribulin, toripalimab, and lenvatinib failed to control the disease failed to control the disease...To our knowledge, this is the first reported use of inavolisib in angiosarcoma. The rapid biochemical and radiological response observed in this PIK3CA-mutated PSA supports early genomic profiling to identify actionable alterations and warrants prospective evaluation of combined phosphoinositide 3-kinase and vascular endothelial growth factor pathway inhibition in refractory angiosarcoma.

A transcriptional signature associated with SARM sensitivity was identified, primarily driven by proliferation-related processes, consistent with a significant decrease in S-phase cell cycle proteins upon treatment in EP0062-sensitive models. In some EP0062-resistant tumors, the combination with palbociclib enhanced the antitumor effect of EP0062, suggesting a potential strategy for metastatic patients with acquired ET resistance.

Our findings suggest HIV-1 dysregulates cervical cell signaling via paracrine mechanisms to phenocopy PIK3CA-activating mutations through IRS1-PI3K-AKT pathway activation. Our findings highlight IRS1 and the PI3K pathway as a potential therapeutic target for cervical cancer in women living with HIV-1.

Notably, low-dose Capivasertib, an AKT inhibitor targeting tumors with PIK3CA/AKT1/PTEN mutation(s), induced senescence selectively in FUCA2-high LUAD irrespective of PIK3CA/AKT1/PTEN/TP53 mutational status, and its combination with the nutraceutical senolytic procyanidin C1 achieved potent and low-toxicity suppression of LUAD across multiple preclinical models. Together, our results uncover the FUCA2-ErbB3 fucosylation-AKT pathway as a central regulator of senescence and propose a FUCA2-guided drug repurposing strategy for LUAD.

Moving forward, the "HER2-positive" designation must be refined through integrated, biomarker-driven frameworks. Incorporating these molecular nuances into prospective clinical trials is essential for optimizing therapeutic de-escalation and overcoming the persistent challenges of resistance in HER2-targeted care.

Due to limited germline and epigenetic data, MSI-H tumors could not be classified as Lynch-associated or sporadic. Overall, MSI-H and MSS CRCs in the Chinese population demonstrate distinct molecular landscapes in terms of TMB, HRD, EBV status, and driver gene alterations, underscoring the molecular heterogeneity of MSI-H CRC and the need for future studies integrating germline and epigenetic data to refine subtype classification.

Future studies should focus on evaluating the efficacy of PI3K inhibitors, alone or in combination with immunotherapy and other targeted treatments, in selected patients. This evaluation should be based on molecular alterations that may predict therapeutic benefit.