FGFR2 mutation

Some known tumor-related genes, such as FGD6, FGFR2 and FZD1, were strongly related to TIAM2 gene. TIAM2 overexpression closely correlated with tumor multiplicity and poor prognosis in resected HCC, thus being a potential therapeutic target.

Inhibition of the RAD51B-EZH2 axis allows the re-expression of functional ERα, making TNBC targetable by endocrine therapy. Consistently, the combination of EZH2 inhibitor with tamoxifen effectively reduces TNBC progression, suggesting that the RAD51B-EZH2 axis is a potential therapeutic target for TNBC.

Four clinical examples illustrated LB-guided therapies. This largest-to-date aSCC cohort reinforces molecular profiling-especially LB-as a key tool for guiding personalized therapy.

Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs. These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases, warranting further investigation in larger cohorts.

Immunotherapy in PSC-associated BTCs appeared safe, with a potential signal of effectiveness. Given the sample size and retrospective design, these results are hypothesis-generating. Together, these results demonstrate the unique biology underlying PSC-associated BTCs, highlighting the need for prospective trials and the development of specialized treatment strategies.

HER2 amplification was associated with worse OS; dMMR and BRCA mutations showed a trend toward improved OS.ConclusionReal world first-line chemoimmunotherapy for advanced BTC achieved outcomes comparable to those in pivotal trials. The ECOG performance status, serum albumin level, and HER2 status were prognostic for OS, supporting the importance of baseline patient selection and molecular profiling in treatment planning.

Of the 85 cases, disease control was achieved in 49 cases, 44 cases of which were biliary tract cancer. FGFR2 might be a promising therapeutic target not only for cholangiocarcinoma with fusion but also for esophagus/stomach cancer and breast cancer with FGFR2 alterations.

BTCs have been traditionally managed with gemcitabine and cisplatin (GC), but this standard of care has shown limited efficacy due to early recurrence, high resistance rates, and molecular heterogeneity...Additionally, novel regimens including nanoliposomal irinotecan and dual ICI combinations represent viable second-line options...Personalized treatment guided by molecular characteristics is now central to improving outcomes. Future efforts must prioritize the identification of biomarkers, clarification of resistance mechanisms, and optimization of multimodal treatment strategies to maximize patient benefit.

The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

For adjuvant treatment, capecitabine (based on the BILCAP trial) and S-1 (from the ASCOT trial) have become standard regimens. Neoadjuvant therapy using gemcitabine-platinum combinations and locoregional strategies such as hepatic artery infusion chemotherapy (HAIC) and yttrium-90 radioembolization (Y-90 TARE) have improved resectability and survival outcomes...FGFR2 fusions, IDH1 mutations, and BRAF V600E mutations can be targeted with inhibitors such as pemigatinib, ivosidenib, and dabrafenib-trametinib, respectively, showing promising response rates in clinical trials...Combination strategies involving PD-1 inhibitors with radiotherapy or anti-angiogenic agents are further expanding the potential for treatment. Future efforts should focus on standardizing resectability criteria, expanding access to molecular profiling, and accelerating Phase III trials.

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target.

These findings highlight a novel cooperativity between FGFR2 and p110α that boosts the effectiveness of inavolisib. The data support advancing precision oncology beyond single biomarkers to complex algorithms utilizing co-occurring alterations, particularly suggesting that combining inavolisib with FGFR2 inhibitors may offer enhanced and more durable responses in PIK3CA/FGFR2-altered tumors.