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

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.

TERT promoter mutations and CDKN2A/B homozygous deletion occur exclusively in high-grade meningiomas, link to unfavorable prognosis, and can serve as independent diagnostic markers for WHO grade 3 meningioma. JAK3 mutation seems also to be associated with high-grade meningiomas and shorter survivals.

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.

BBO-8520 exerted more potent and sustained inhibition of KRAS G12C and anti-tumor activity in vitro and in vivo compared with sotorasib, a KRAS G12C (OFF)-only inhibitor...Moreover, in some contexts, disruption of RAS-PI3Kα further increased the anti-tumor activity of BBO-8520 monotherapy. These results reveal mechanistic differences between KRAS (ON) and (OFF) inhibitors, highlight the importance of PI3Kα-AKT signaling in driving resistance to KRAS inhibition in lung cancer, and suggest combination strategies that suppress PI3Kα-AKT to improve the response to KRAS inhibitors.

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.

The efficacy of JWJCJ in treating chronic constipation in PD involves the targets SRC, PIK3R1, JUN, TP53, STAT3, PIK3CA, EGFR, ESR1, MAPK1, and AKT1 domains. These findings provide theoretical basis for the clinical application of JWJCJ decoction in the treatment of chronic constipation in PD.