FGFR2 fusion as the key to targeted therapy – a case report with a diagnostic turning point

Summary

Non-small cell lung cancer is currently becoming a highly heterogeneous group of diseases from a therapeutic perspective, thanks to the availability of tumor tissue examination using next-generation sequencing (NGS). A positive consequence of this development is the differentiation of treatment protocols based on the results of predictive factor testing. Targeted therapy, which is changing the clinical landscape of many of these diseases as well as the fates of those affected, is becoming a beacon of hope for nearly half of patients with lung adenocarcinomas. Genetic alterations in FGFR genes, which regulate proliferation, differentiation, angiogenesis, and apoptosis, can activate relevant signaling pathways and trigger the growth of tumors driven by these mechanisms. While these alterations are most commonly found in cholangiocarcinomas, they are also identified in a small subgroup of patients with lung adenocarcinomas. Targeted therapy with FGFR tyrosine kinase inhibitors, particularly in the presence of the FGFR3-TACC3 gene fusion, is capable of inducing long-term remission even in advanced disease previously treated with multiple modalities, as evidenced by our observations. The aim of our case reports is to demonstrate that cases defying standard procedures can emerge in clinical practice. Definitive diagnosis may evolve over time; therefore, it is essential to evaluate all findings critically. The dynamics of the clinical picture require continuous reassessment, repeated biopsies, and he utilization of modern molecular profiling methods (NGS) to ensure the most accurate diagnosis and optimal treatment strategy. The journey toward targeted therapy can be arduous and may be preceded by immunotherapy with a favorable clinical response.

Keywords:

Next-generation sequencing – pemigatinib – non-small-cell lung carcinoma – FGFR2 fusion – pancreatobiliary adenocarcinoma