The Met pathway: master switch and drug target in cancer progression.
It has been recognized for more than a century that most tumors tend to become more aggressive in clinical behavior over time, although this time course may be variable. This phenomenon has been termed "cancer progression," a process that appears to develop in a stepwise fashion through qualitatively different stages. Cancer progression relies on the ability of neoplastic cells to abandon their primary site of accretion, trespass tissue boundaries, and penetrate into the vasculature to colonize and repopulate distant sites. Among the various properties associated with cancer progression, the acquisition by neoplastic cells of the capacity to invade locally and to metastasize is of great clinical significance, and is still the fundamental definition of malignancy. This process represents the aberrant counterpart of a physiological morphogenetic program, known as invasive growth, occurring during embryo development and, in some instances, in adulthood for the generation and maintenance of normal organ complexity and architecture. Here we summarize some of the strategies adopted to inhibit cancer cell growth and spreading. We also review the current findings about cancer and metastasis inhibitors. As we suggest possible directions for drug development, we propose the receptor for the hepatocyte growth factor, Met, as an ideal target for tackling cancer progression.
Mazzone
Massimiliano
M
Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, Strada Provinciale 142, km 3.95, I-10060 Candiolo (Torino), Italy. massimiliano.mazzone@ircc.it
Comoglio
Paolo M
PM
D018450:Disease Progression; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met