| Autor: |
Lau DK; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.; School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia.; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.; Department of Oncology, Monash Health, Clayton, VIC 3168, Australia., Collin JP; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.; School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia., Mariadason JM; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.; School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia. |
| Abstrakt: |
Recent advances in the treatment of gastric cancer (GC) with chemotherapy, immunotherapy, anti-angiogenic therapy and targeted therapies have yielded some improvement in survival outcomes; however, metastatic GC remains a lethal malignancy and amongst the leading causes of cancer-related mortality worldwide. Importantly, the ongoing molecular characterisation of GCs continues to uncover potentially actionable molecular targets. Among these, aberrant FGFR2-driven signalling, predominantly arising from FGFR2 amplification, occurs in approximately 3-11% of GCs. However, whilst several inhibitors of FGFR have been clinically tested to-date, there are currently no approved FGFR-directed therapies for GC. In this review, we summarise the significance of FGFR2 as an actionable therapeutic target in GC, examine the recent pre-clinical and clinical data supporting the use of small-molecule inhibitors, antibody-based therapies, as well as novel approaches such as proteolysis-targeting chimeras (PROTACs) for targeting FGFR2 in these tumours, and discuss the ongoing challenges and opportunities associated with their clinical development. |
