Prostate cancer: potential targets of anti-proliferative and apoptotic signaling pathways.
Prostate cancers are genetically and phenotypically heterogenous. The heterogeneous nature of prostate cancer may be a consequence of mutations in different cell types (basal stem, transit amplifying or luminal cells) resulting in different malignant maturation pathways. One consistent characterization of these cancers, however, is their eventual progression to a hormonal refractory state. The development of effective novel therapeutic strategies requires an understanding of the mechanisms for the development of such a refractory state. Targeting proliferative and survival pathways provides a rationale for drug design and development for hormone refractory prostate cancer. Prostate cancer cells, however, develop an enhanced redundancy in downstream survival signaling. Hence, new combinational therapies must be developed with the understanding that compensatory mechanisms evolve under selective pressure.
Uzgare
Aarti R
AR
Anti-Cancer Drug Discovery/Development Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB 1M44, Baltimore, MD 21231-1000, USA. auzgare@jhu.edu
Isaacs
John T
JT
D017209:Apoptosis; D002455:Cell Division; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D015398:Signal Transduction