Gastrointestinal stromal tumors: who should get imatinib and for how long?

The application of imatinib for the treatment of GIST remains a remarkable illustration of the ability and promise of targeted molecular therapy. It is gradually becoming evident that the benefit of imatinib depends on the complex interplay between mutational variations that govern tumor sensitivity to the drug, and biological variables that drive clinical outcome. Evidence is mounting that only a select fraction of patients in the adjuvant setting may benefit from imatinib. Unfortunately, most patients with metastatic disease develop resistance to imatinib, as occurs in other diseases treated with kinase inhibitors. Thus, although imatinib has demonstrated that kinase inhibitor therapy is an integral component of cancer care, it has also revealed the challenges in treating a dynamic cancer with a static monotherapy. As greater insight is gained into when imatinib does not help, it will uncover the obvious next pathway in cancer treatment, namely individualized, genotype-directed therapy that is modulated according to the genetic and immunologic landscape of the tumor.