c-Kit expression in human normal and malignant stem cells prognostic and therapeutic implications

The human stem cell factor/c-Kit signaling pathway is pivotal for the survival of embryonic, foetal and adult stem cells and for their fundamental role in generating healthy functioning cell and tissue types during embryonic, foetal and adult life. Common biological features between human stem cells and cancer cells include (A) self-renewal, (B) extensive capacity of proliferation, (C) migration to and homing at distant sites and (D) resistance to toxic agents. Given these shared attributes, cancer was proposed to originate from transforming mutation(s) in normal stem cells that dysregulate their physiological programs. This theory has been recently supported by the findings that among all malignant cells within a particular tumour, only cell fraction expressing stem cell markers such as c-Kit named 'cancer stem cells' has the exclusive potential to generate tumour cell population. The involvement of c-Kit and its mutation in various haematological malignancies and solid tumours are reviewed. The impacts of dysregulated c-Kit as oncogenic tyrosine kinase on autocrine stimulation and resistance to chemotherapy of cancer stem cells are evaluated. The significance and efficacy of molecular therapeutic targeting of c-Kit signaling pathway in the management of patients with c-Kit-positive malignancies are appraised. (C) 2008 Elsevier Ltd. All rights reserved.