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In this review, we discuss the rationale for and development of KIT tyrosine kinase inhibitors for the treatment of human malignancies.<\/jats:p><jats:p>MATERIALS AND METHODS: Studies were identified through a MEDLINE search, review of bibliographies of relevant articles, and review of abstracts from national meetings.<\/jats:p><jats:p>RESULTS: Four tyrosine kinase inhibitors that have activity against KIT are currently being used in clinical trials, and one, STI571, has recently been approved by the United States Food and Drug Administration for treating patients with chronic myelogenous leukemia. The role of KIT inhibitors in treating KIT-positive malignancies is reviewed.<\/jats:p><jats:p>CONCLUSION: Targeted therapy to inhibit the kinase activity of KIT is a rational approach to the treatment of KIT-positive malignancies. Two key factors are the potency of a given inhibitor and the relative contribution of KIT activation to the growth of the tumor. Given our current understanding of KIT activity in human malignancy, the best candidate diseases for treatment with KIT inhibitors are GIST, mastocytosis, seminoma and possibly some cases of AML. Additionally, KIT inhibitors may play an adjunctive role in diseases such as small-cell lung cancer, in which KIT activation is secondary to ligand binding rather than an acquired mutation.<\/jats:p>","DOI":"10.1200\/jco.2002.20.6.1692","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T08:46:10Z","timestamp":1487925970000},"page":"1692-1703","source":"Crossref","is-referenced-by-count":489,"title":["Inhibition of KIT Tyrosine Kinase Activity: A Novel Molecular Approach to the Treatment of KIT-Positive Malignancies"],"prefix":"10.1200","volume":"20","author":[{"given":"Michael C.","family":"Heinrich","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Division of Hematology\/Oncology and Department of Pathology and Laboratory Medicine, Oregon Health and Science University; and Portland Veterans Affairs Medical Center, Portland, OR."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles D.","family":"Blanke","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Hematology\/Oncology and Department of Pathology and Laboratory Medicine, Oregon Health and Science University; and Portland Veterans Affairs Medical Center, Portland, OR."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Druker","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Hematology\/Oncology and Department of Pathology and Laboratory Medicine, Oregon Health and Science University; and Portland Veterans Affairs Medical Center, Portland, OR."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Corless","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Hematology\/Oncology and Department of Pathology and Laboratory Medicine, Oregon Health and Science University; and Portland Veterans Affairs Medical Center, Portland, OR."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1-105196","doi-asserted-by":"crossref","unstructured":"Yarden Y, Kuang W-J, Yang-Feng T, et al: Human proto-oncogene c-kit: A new cell surface receptor tyrosine kinase for an unidentified ligand. 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