Role of small-molecule kit receptor tyrosine kinase inhibitors in the treatment of small-cell lung cancer.
The prognosis of extensive-stage small-cell lung cancer (SCLC) has changed little in the past 3 decades, despite the documentation of high response rates to multiple chemotherapeutic regimens. Increasing the dose or the dose intensity of standard chemotherapy has increased toxicity without a significant improvement in outcome. However, our understanding of the biology of this disease has dramatically changed over the past 30 years, and this understanding has resulted in the identification of novel therapeutic targets. Evidence supporting the Kit growth factor receptor tyrosine kinase as a therapeutic target in SCLC is detailed. The properties of small-molecule Kit inhibitors currently in clinical development, as well as their efficacy in preclinical SCLC studies, are presented. The rationale for combining small-molecule Kit inhibitors with standard chemotherapy in clinical trials for extensive-stage SCLC is discussed.
Lloyd
Katherine P
KP
Medical College of Virginia/Virginia Commonwealth University and McGuire VA Medical Center, Richmond 23249, USA.
Krystal
Geoffrey W
GW