Collectively, our analysis describes the driver genes and mutation characteristics in SCC. The multi-cohort and network-based framework employed in this study identifies candidate hub genes that warrant further clinical investigation in cervical cancer.

P2, N=160, Not yet recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Upon PI3Kα inhibition with alpelisib, insulin engaged bypass signaling that partially counteracted downstream suppression. MEK inhibition alone suppressed the growth of PIK3CA mutant cells, and dual targeting of PI3K and MAPK signaling produced greater growth suppression than either single agent alone under insulin-stimulated conditions. Collectively, these findings reveal mutation-specific adaptive signaling and support combined PI3Kα and MAPK pathway inhibition as a strategy to improve therapeutic efficacy in PIK3CA mutant breast cancer.

Additionally, cytokine profiles (IL-2, IL-6, IFN-γ and IL-10) were altered when alpelisib-treated macrophages were cocultured with CD4+ T cells under either antigen-specific or polyclonal activation conditions, indicating that the inhibitor modifies both differentiation and subsequent effector interactions of the macrophages. Thus, alpelisib induces lasting effects on macrophage differentiation and function, with potential implications in tumor-associated macrophages that develop under M-CSF or GM-CSF-rich cancer microenvironments.

Particular emphasis is placed on the translation of molecular diagnostics into clinical decision-making, including patient selection, resistance mechanisms, and sequencing strategies within evolving precision oncology frameworks. Ongoing clinical and translational research will be critical to refine combination strategies, overcome resistance mechanisms, and identify predictive biomarkers to further optimize patient outcomes.

P1, N=30, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Sep 2028 --> Jul 2027 | Trial primary completion date: Sep 2028 --> Jul 2027

P1/2, N=24, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> May 2027

Citation burst analysis indicated an early focus on molecular mechanisms and gene mutations, while recent studies have shifted toward precision medicine, including liquid biopsy, advanced breast cancer subtypes, and targeted therapies such as alpelisib and fulvestrant, reflecting evolving priorities toward personalized treatment. This bibliometric study identifies six key research hotspots in PIK3CA and breast cancer, demonstrating the transition from basic mechanisms to clinical applications. Recent research trends, including liquid biopsy, advanced subtypes, and combination therapies, are closely tied to precision medicine and individualized treatment approaches.

Normal baseline glycemic indices do not reliably exclude the risk of severe toxicity. Early metabolic assessment, close glucose monitoring, prompt interruption of inavolisib when clinically indicated, and rapid insulin-based management are essential for timely recognition and safe clinical care.

In xenografts, PAC-XL outperformed cetuximab, BGT226 and alpelisib, including complete regressions, while reducing hyperglycemia and weight loss caused by systemic PI3K/mTOR inhibition. These findings establish targeted delivery of PI3K/mTOR inhibitors as a strategy to enhance efficacy while improving tolerability in HNSCC.

P2, N=130, Active, not recruiting, Borstkanker Onderzoek Groep | Trial primary completion date: Jan 2026 --> May 2026

P1, N=30, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting