PIK3CA mutation

Lung adenocarcinomas with PIK3CA mutations exhibit distinct clinicopathological characteristics in terms of gender, age, smoking history, differentiation degree, and clinical stage. Acquired drug resistance in lung adenocarcinoma may be accompanied by PIK3CA mutations, but PIK3CA mutation is not the main mechanism of targeted therapy resistance in lung adenocarcinoma patients.

Increased IRS2 abundance also correlates with PI3K pathway inhibitor resistance across PI3K mutant cancer cell lines from a variety of tissues. The clinical relevance of these findings is highlighted by the frequency of PI3K mutations in cancer and the identification of a new target to address the challenges associated with prior efforts to block the reactivation of PI3K signaling during PI3K inhibition.

Inhibiting PI3K enhanced sensitivity to mutant-specific KRAS inhibitors in PDAC cells, including in cells with clinically identified PIK3CA mutations. These findings refine RAS-PI3K signaling paradigms, reveal that PI3K-driven wild-type RAS activation drives resistance to KRAS inhibition, and illuminate avenues for augmenting KRAS-targeted therapies in PDAC.

Treatments include surgery, radiation, and chemotherapy, with ongoing trials investigating agents like cetuximab, cisplatin, and Tazemetostat. Tazemetostat, targeting KMT2D-related DNA (deoxyribonucleic acid) methylation, and cetuximab, targeting the PIK3CA signaling cascade, may offer therapeutic benefits. Further research on mutation-specific therapies could improve treatment strategies.

Integrating germline PGx with somatic profiling reveals that actionable germline variants are nearly universal among patients with cancer in our cohort, extending beyond tumor-specific therapy to encompass toxicity and supportive care management. Routine implementation of combined germline and somatic sequencing in oncology could enhance therapeutic precision, minimize adverse effects, and inform individualized treatment decisions.

P3, N=420, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Apr 2026 --> Nov 2026

P=N/A, N=8, Completed, HealthPartners Institute | Active, not recruiting --> Completed | N=15 --> 8

Additionally, the mutant group exhibited higher TMB (p < 0.05), poorer prognosis in high-MSI patients (p = 0.04), and frequent co-mutations in TP53 and PIK3CA. SMARCA4 mutation is an independent adverse prognostic factor in breast cancer (HR = 1.6, p = 0.02), linked to enhanced metastasis, altered HER2/HR prognostic value, and genomic instability, with potential as a prognostic biomarker.

These findings suggest that incorporating ancestry into screening, trials, and precision oncology may improve equity, though outcome-linked prospective studies and implementation research are warranted.

FGFR inhibition reverses these changes and synergizes with anti-PD-1 therapy to enhance antitumor immune responses and establish durable immune memory. Collectively, these findings identify FGFR signaling as a key driver of therapeutic resistance and immune escape in SEC and support FGFR-targeted combination strategies.

Following tamoxifen induction, blood blister-like lesions developed on the tail, ear, and paw in 86.9% (53/61) of mice harboring at least one Pik3caH1047R allele, whereas no lesions were observed in mice lacking the mutant allele (0/13, P < 0.0001)...Together, these findings demonstrate that PIK3CA activation initiates highly penetrant vascular malformations, whereas p53 loss promotes their rare neoplastic transformation. This model provides mechanistic and translational insight into how benign PIK3CA-mutant vascular malformations may progress toward vascular malignancy and offers a platform for studying biomarkers and therapeutic strategies to prevent this transition.

Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy.