New developments in management of gastrointestinal stromal tumors: regorafenib, the new player in the team

Abstract:

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and the most frequent single type of sarcoma, at least in some geographical regions. They arise from the interstitial cells of Cajal (or a common progenitor cell). The vast majority of GISTs are characterized by oncogenically activating mutations in the KIT or platelet-derived growth factor receptor alpha (PDGFRA) receptor tyrosine kinase genes. This molecular feature has been successfully exploited for therapeutic purposes, and as of a decade ago, GISTs have become the prototype of a solid tumor that can be targeted with small molecule kinase inhibitors. Imatinib mesylate (Gleevec^®/Glivec^®) benefits more than 85% of patients with unresectable and/or metastatic GIST. Unfortunately, the majority of patients develop resistance to imatinib within the first 2 years of treatment and new therapeutic options are needed. Although the broad-range kinase inhibitor sunitinib malate (Sutent^®) has been the second-line therapy approved by the US Food and Drug Administration since 2006, it was not until recently (February 2013) that regorafenib (Stivarga^®) was approved as a third-line therapeutic agent for GIST. This review summarizes the development process of regorafenib for GIST and highlights its biochemical, pharmacologic, and clinical properties.

Keywords::

• gastrointestinal stromal tumors
• GIST
• regorafenib

Disclosure

The authors report no conflicts of interest in this work.