Receptor tyrosine kinases as rational targets for prostate cancer treatment: Platelet-derived growth factor receptor and imatinib mesylate

被引:37
作者
George, DJ [1 ]
机构
[1] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA
关键词
D O I
10.1016/S0090-4295(02)01589-3
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Over the past 15 years, numerous signal transduction pathways have been elucidated whose dysregulation may play an important role in the growth and survival of cancer cells. The success of imatinib mesylate (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ), a small molecule that inhibits the activation of the BCR-Abl oncogene in the treatment of chronic myelogenous leukemia, has demonstrated how effective targeted strategies can be when properly applied. With the hope of selectively targeting other critical components of cancer growth and survival while minimizing toxicity to the host, numerous strategies have been developed to inhibit receptor tyrosine kinases for various growth factors commonly expressed by cancer cells. Success of targeted inhibitors is inherently dependent on the proper selection of patients whose tumors are dependent on these growth factor pathways. Unfortunately, in prostate cancer, such selection has been a difficult-to-impossible task to date. Because of the vast number of mutational events, it is difficult to demonstrate that any particular growth factor signaling pathway is critical. In addition, because of the type (mostly bone only) and nature (usually small foci) of metastases, limited access to tumor tissue in the advanced cancer population has hampered attempts to characterize patients by their molecular features or phenotype. This article will focus on defining alternative criteria for a rational drug target and novel study designs for testing these agents in prostate cancer. In particular, the neoadjuvant setting represents a unique opportunity for new drug development in prostate cancer. An example of a neoadjuvant study testing, imatinib mesylate, is presented to display the advantages and limitations of this study design.
引用
收藏
页码:115 / 121
页数:7
相关论文
共 37 条
[1]   MALIGNANT EPITHELIAL-CELLS IN PRIMARY HUMAN LUNG CARCINOMAS COEXPRESS INVIVO PLATELET-DERIVED GROWTH-FACTOR (PDGF) AND PDGF RECEPTOR MESSENGER-RNAS AND THEIR PROTEIN PRODUCTS [J].
ANTONIADES, HN ;
GALANOPOULOS, T ;
NEVILLEGOLDEN, J ;
OHARA, CJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (09) :3942-3946
[2]   Expression of platelet-derived growth factor (PDGF)-A, PDGF-B and the PDGF-alpha receptor, but not the PDGF-beta receptor, in human malignant melanoma in vivo [J].
Barnhill, RL ;
Xiao, M ;
Graves, D ;
Antoniades, HN .
BRITISH JOURNAL OF DERMATOLOGY, 1996, 135 (06) :898-904
[3]   Growth factors and their receptors: New targets for prostate cancer therapy [J].
Barton, J ;
Blackledge, G ;
Wakeling, A .
UROLOGY, 2001, 58 (2A) :114-122
[4]  
BETSHOLTS C, 1986, NATURE, V323, P226
[5]   PLATELET-DERIVED GROWTH-FACTOR EXPRESSION AND STIMULATION IN HUMAN MENINGIOMAS [J].
BLACK, PM ;
CARROLL, R ;
GLOWACKA, D ;
RILEY, K ;
DASHNER, K .
JOURNAL OF NEUROSURGERY, 1994, 81 (03) :388-393
[6]  
BLANKE CD, 2001, ASCO, V20, pA1
[7]  
Buchdunger E, 1996, CANCER RES, V56, P100
[8]  
Buchdunger E, 2000, J PHARMACOL EXP THER, V295, P139
[9]  
CHAUDHRY A, 1992, CANCER RES, V52, P1006
[10]   Tyrosine kinases expressed in vivo by human prostate cancer bone marrow metastases and loss of the type 1 insulin-like growth factor receptor [J].
Chott, A ;
Sun, Z ;
Morganstern, D ;
Pan, J ;
Li, T ;
Susani, M ;
Mosberger, I ;
Upton, MP ;
Bubley, GJ ;
Balk, SP .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (04) :1271-1279