TY - JOUR
T1 - The role of HGF/c-Met signaling in prostate cancer progression and c-Met inhibitors in clinical trials
AU - Varkaris, Andreas
AU - Corn, Paul G.
AU - Gaur, Sanchaika
AU - Dayyani, Farshid
AU - Logothetis, Christopher J.
AU - Gallick, Gary E.
N1 - Funding Information:
CJL were supported by SPORE 1P50 CA14038801 and two awards from Prostate Cancer Foundation (“Mechanism of Resistance to Androgen Biosynthesis Inhibition in Castrate-Resistant Prostate Cancer Bone Metastasis” and “Individualized Microenvironment Targeted Therapy for Prostate Cancer Bone Metastases: Simultaneous Evaluation of Multiple Therapeutic Targets”). FD was supported by NIH grant T32 CA009666. SG was supported by UTHealth Innovation for Cancer Prevention Research Pre-doctoral Fellowship, The University of Texas School of Public Health --Cancer Prevention and Research Institute of Texas grant # RP101503.
Funding Information:
The project described was supported by Grant Number P50 CA140388 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
PY - 2011/12
Y1 - 2011/12
N2 - Introduction: An increasing number of basic, translational and clinical studies demonstrate the importance of the protein tyrosine kinase receptor, c-Met, in the progression of prostate cancer. c-Met is overexpressed in primary prostate cancers, further increased in expression in bone metastases and is associated with the development of castrate-resistant disease. Because of its importance as a target, c-Met inhibitors have reached clinical trial for advanced, castrate-resistant prostate cancer. Areas covered: In this review, altered expression of c-Met and hepatocyte growth factor in prostate tumors and the microenvironment and how they contribute to growth and invasion of prostate cancer cells is described. Next, preclinical studies providing the support for use of c-Met inhibitors are discussed. Finally, early promising results from c-Met inhibitors in clinical trial, and future prospects for c-Met inhibitors in the treatment of advanced stage prostate cancer, are discussed. Expert opinion: An emerging theme in treating metastatic prostate cancer is the requirement to target both the epithelial and stromal compartments. Results from clinical trials suggest that inhibitors of c-Met that block stromal-mediated c-Met activation in prostate tumors may be important therapeutic agents in at least a subset of patients with metastatic prostate cancer. However, as many of the inhibitors have multiple targets, the efficacy of targeting c-Met alone remains to be determined.
AB - Introduction: An increasing number of basic, translational and clinical studies demonstrate the importance of the protein tyrosine kinase receptor, c-Met, in the progression of prostate cancer. c-Met is overexpressed in primary prostate cancers, further increased in expression in bone metastases and is associated with the development of castrate-resistant disease. Because of its importance as a target, c-Met inhibitors have reached clinical trial for advanced, castrate-resistant prostate cancer. Areas covered: In this review, altered expression of c-Met and hepatocyte growth factor in prostate tumors and the microenvironment and how they contribute to growth and invasion of prostate cancer cells is described. Next, preclinical studies providing the support for use of c-Met inhibitors are discussed. Finally, early promising results from c-Met inhibitors in clinical trial, and future prospects for c-Met inhibitors in the treatment of advanced stage prostate cancer, are discussed. Expert opinion: An emerging theme in treating metastatic prostate cancer is the requirement to target both the epithelial and stromal compartments. Results from clinical trials suggest that inhibitors of c-Met that block stromal-mediated c-Met activation in prostate tumors may be important therapeutic agents in at least a subset of patients with metastatic prostate cancer. However, as many of the inhibitors have multiple targets, the efficacy of targeting c-Met alone remains to be determined.
KW - C-Met
KW - HGF
KW - Prostate cancer
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U2 - 10.1517/13543784.2011.631523
DO - 10.1517/13543784.2011.631523
M3 - Review article
C2 - 22035268
AN - SCOPUS:81555228393
SN - 1354-3784
VL - 20
SP - 1677
EP - 1684
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 12
ER -