Combination docetaxel and platelet-derived growth factor receptor inhibition with imatinib mesylate in prostate cancer.
The burden of metastatic disease in prostate cancer is largely distributed to bone in the form of osteoblastic metastases. Interactions between malignant epithelial cells of prostate cancer and the bone microenvironment are implicated in the progression of prostate cancer. Because prostate cancer cells in bone metastases express the platelet-derived growth factor receptor (PDGFR), it is possible that inhibition of PDGFR can be an effective means of altering the clinical course of prostate cancer. Preclinical data suggest that preferential expression of PDGFRs in endothelial cells of tumor vasculature in experimental prostate cancer bone metastases is an important target for combination therapy incorporating the PDGFR inhibitor imatinib mesylate. Clinical trials combining imatinib and docetaxel are under way in the metastatic and neoadjuvant settings. Clinical and translational data from these studies are likely to provide additional insights into the role of imatinib in combination therapy for prostate cancer.
Mathew
Paul
P
University of Texas M.D. Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, 77030, USA.
Fidler
Isaiah J
IJ
Logothetis
Christopher J
CJ
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D000077143:Docetaxel; D016503:Drug Delivery Systems; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D010879:Piperazines / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000008:administration & dosage; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D043823:Taxoids / Q000008:administration & dosage
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D043823:Taxoids; D000077143:Docetaxel; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor