FGFR2 S252W

P2, N=46, Active, not recruiting, National Cancer Center, Japan | Recruiting --> Active, not recruiting

Through this patient, we demonstrate that advanced-metastatic GBC with FGFR alterations can be maintained on anti-FGFR therapy for prolonged periods of time, with improved survival. Therefore, we endorse the need for comprehensive genomic profiling in advanced-metastatic GBC and the need to study the role of FGFR inhibitors as a viable treatment option in these patients.

Targeted next-generation sequencing of these five tumor components demonstrated identical mutations in PTEN (p.R130G), PIK3CA (p.G1049S), FGFR2 (p.S252W), and FBXW7 (p.R689Q), suggesting that all components arose from a common precursor. The endometrial endometrioid carcinoma harbored additional exclusive mutations involving PIK3CA (p.H1048R) and CTNNB1 (p.S37F).

Finally, we developed a tumor slice culture system and demonstrated the synergy between immune checkpoint blockade and targeted therapy in triple-negative breast cancer (TNBC). These data extend our understanding of epigenetic reprogramming and epigenetics-based therapies.

It is also shown that FGFR2 positively regulates PD-L1 and that a combination of FGFR2 inhibition and immune checkpoint blockade kills cancer cells. These data suggest that the mouse models mimic human breast cancers and can be used to identify actionable therapeutic targets.

Moreover, FGFG2 expression and genetic aberrations showed clinical associations with patient survival in several cancers, indicating their potential for application as new tumor markers and therapeutic targets. This study showed the full FGFR2 alteration spectrum and provided a broad molecular perspective of FGFR2 in a comprehensive manner, suggesting some new directions for clinical targeted therapy of cancers.

Food and Drug Administration (FDA) has approved Balversa (erdafitinib) for metastatic bladder cancer treatment, and more FGFR inhibitors are currently being evaluated clinically in many other cancer types, including lung cancer...Hopefully, more patients with other FGFR mutations may benefit from FGFR inhibitors as well, which needs further clinical investigation. Meanwhile, the exclusive relationship between druggable FGFR mutations and other actionable variations in lung cancers defines a unique molecular subtype, extending the number of patients who can benefit from targeted therapy.