Evolving Therapeutic Strategies in Gastrointestinal Stromal Tumors

Abstract

Gastrointestinal stromal tumors (GISTs) account for 20% of sarcomatous tumors and 1−2% of primary gastrointestinal cancers. When localized and operable, GISTs have a favorable prognosis with a five-year overall survival of around 80%. In the metastatic setting, the prognosis is poor with limited therapeutic options. Standard treatments include four tyrosine kinase inhibitors (TKIs) for _KIT_-mutated GIST and one for _PDGFRA_-mutated GIST. The evolution of molecular oncology and the widespread use of next-generation sequencing have already allowed new therapeutic approaches and are expected to lead to further treatment options. The emergence of resistance due to secondary mutations caused by selective pressure from TKIs remains a significant challenge. Tailoring treatments through repeated biopsies and non-invasive liquid biopsies at progression could be a promising approach. Ongoing investigations into new molecules with broader KIT inhibition may also reshape the treatment landscape. Finally, combination therapies may overcome the emergence of resistance mechanisms. This review provides an overview of the epidemiology and biology of GISTs and explores current and future management options. PEER REVIEWED ARTICLE