FGFR2 mutation

Molecular testing has become an essential component of modern iCCA management. Broad, early, and technically integrated molecular profiling-ideally performed at initial diagnosis and interpreted in an interdisciplinary (molecular) tumor board-is critical to fully realize the potential of precision oncology in BTC.

P3, N=138, Not yet recruiting, TransThera Sciences (Nanjing), Inc.

Initial chemotherapy combined with immune checkpoint inhibitors achieved short-term stability, but the disease eventually progressed. Genetic testing revealed an Fibroblast growth factor receptor 2 (FGFR2) mutation, leading to a switch to targeted therapy with lenvatinib combined with capecitabine, demonstrating the value of targeted therapy in the management of rare, refractory sebaceous carcinoma.

In molecular level, PLNTY exhibits alterations in the MAPK pathway; while its DNA methylation profile demonstrates diversity. Most patients achieved seizure-free outcomes postoperatively, indicating a favorable prognosis.

Despite a broader availability of EMP in advanced CCA, patient access to targeted treatments remains suboptimal. Our results demonstrate that such treatments can dramatically impact on OS, Therefore, strategies aiming at increasing the access to (and accelerate the availability of) targeted treatments are warranted.

In the first-line setting, gemcitabine plus cisplatin (GemCis) chemotherapy served as the long-standing standard of care; subsequently, TOPAZ-1 and KEYNOTE-966 established GemCis plus durvalumab or pembrolizumab as the current standard. For patients who progressed after frontline therapy and lack actionable alterations, fluoropyrimidine plus oxaliplatin and fluoropyrimidine plus liposomal irinotecan are recommended second-line options, supported by ABC-06 and NIFTY, respectively...Although recent advances have improved clinical outcomes in patients with advanced BTC, median overall survival remains around 1 year, underscoring the need for further therapeutic innovation. This review provides a comprehensive overview of the current standards of care and highlights emerging therapeutic strategies for advanced BTC.

In vitro pharmacological inhibition of FGFR2 with a selective inhibitor Futibatinib further demonstrated that it inhibited DLBCL cell growth, cell proliferation, induced cell cycle arrest, promoted cell apoptosis. Further in vivo study found that combination of Futibatinib with chemotherapy displayed better anti-tumor activity relative to single drug therapy in DLBCL treatment.Collectively, our data highlight the importance of considering the GALNT3-FGFR2-MAPK signaling axis as an attractive therapeutic target for lymphomagenesis.

Pooled positive selection screens identified 474 activating and 738 mutations mediating resistance to the FGFR inhibitors pemigatinib and futibatinib, together revealing 301 druggable FGFR mutations analogous to a strong PS3/BS3 evidence level. The functional screens identified 97% of acquired resistance mutations in clinical trials. Our comprehensive catalog of every druggable mutation in the FGFR kinase domains is readily available for clinical decision support.

These findings suggest that tinengotinib might have activity in patients with cholangiocarcinoma with FGFR2 fusions that progressed following FGFR inhibitor therapy. Anti-tumour activity was also observed in patients with other FGFR alterations. The data from this phase 2 study supported the initiation of a phase 3 registration trial.

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.