PIK3CA mutation

In BCs with alterations in the AKT/PIK3CA pathway, capivasertib, alpelisib, and inavolisib have recently improved progression-free survival (PFS). Inavolisib (GC0077) differs from the other drugs targeting this pathway by its high potency and tolerability when combined with endocrine therapy, mostly with fulvestrant, and a CDK4/6 inhibitor. Its recent use in the first-line combined treatment for advanced HR+/HER2-negative BC has shown a PFS benefit compared to placebo in the INAVO120 trial, suggesting its role as a valid treatment option in PIK3CA-mutated patients. Further studies are warranted to confirm these results in terms of prolonging efficacy and maintaining durable responses - with a manageable safety profile - in clinical practice.

We consider ET suitability to be the clinical assessment of whether a patient could benefit from ET, where benefit is defined not solely by tumor response but by a clinically relevant constellation of characteristics and markers possibly predicting the durability of disease response and symptom control. Several unresolved questions remain regarding issues such as disease heterogeneity, optimal treatment sequencing, and biomarker precision, but further work and ongoing studies will help to support the evolution of guidelines and provide clarity around the effective application of this quickly developing field to daily clinical practice.

Furthermore, STC2 knockdown reduced anoikis-related apoptotic rates in an MDA-MB-231-based anoikis-mimic model in vitro. This study established an anoikis-related gene signature that may improve prognostic stratification and reflect immunotherapy-related features in TNBC.

P1, N=90, Recruiting, Cogent Biosciences, Inc. | Not yet recruiting --> Recruiting | Initiation date: Feb 2026 --> Jun 2026

Clinically, two patients died within 3-9 months, while one remains clinically stable despite radiological progression. DHG-H3 K27 represents a rare hemispheric glioma subgroup sharing molecular and epigenetic features of DMG-H3 K27 without midline involvement, underscoring biological heterogeneity and the importance of integrated molecular classification.

These findings highlight the complementary and non-redundant roles of somatic liquid biopsy and germline analyses. Rather than indicating diagnostic equivalence, the results show that each approach captures distinct but clinically relevant genomic information. The inclusion of ONT long-read sequencing may improve the characterization of inherited variants, particularly structural variants and phasing and may support more comprehensive risk assessment and therapeutic planning.

The high prevalence of HPV underscores its etiological significance in CC. These findings contribute to a deeper understanding of the molecular mechanisms underlying CC in this population and may support the development of targeted therapeutic strategies for high-risk individuals. Future prospective studies and functional analyses are warranted to validate the clinical significance of these mutations and clarify their role in disease progression.

Methods We derived a novel PDX from a patient with hormone receptor negative, HER2-positive IBC refractory to neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP)...We performed short-tandem repeat (STR) profiling, plotted tumor growth curves for mice treated with alpelisib/everolimus vs. untreated, and immunohistochemistry (IHC), and performed clinical genomic assays...Conclusion We established a PDX of a HER2-positive IBC tumor with a PIK3CA hotspot mutation (H1047R) refractory to TCHP. Targeting the PI3K/mTOR pathway may be useful to overcome resistance in HER2-positive IBC with a H1047R mutation in PIK3CA.

Notably, the mean duration of disease progression following EGFR-TKI initiation did not differ significantly between patients with EGFR exon 21 p.L858R mutation and those with EGFR 19-Del. Our study reveals the heterogeneity of compound EGFR mutations, and characterizes the spectrum of acquired resistance mutations to EGFR TKIs.

Recent clinical trials (Axi-STS, TAPPAS) demonstrated that single-agent anti-angiogenic inhibitors (axitinib, pazopanib) achieve modest efficacy (median progression-free survival (PFS) 3.0-4.3 months, response rates 5-13%), underscoring angiosarcoma's complex, multipathway-driven pathogenesis. Environmental exposures (vinyl chloride, thorotrast, radiation) drive distinct angiosarcoma subtypes with subtype-specific mutational profiles. We propose that precision-medicine approaches integrating molecular stratification, pathway crosstalk analysis, and biomarker-guided combination therapies represent the rational next steps to overcome therapeutic resistance and improve clinical outcomes in this lethal malignancy.

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.

P1, N=54, Recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2026 --> Jun 2028 | Trial primary completion date: May 2026 --> Mar 2028