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Cell Signaling Modifiers in Prostate Cancer

Chen, Franklin L. MD*; Armstrong, Andrew J. MD*†; George, Daniel J. MD*†

doi: 10.1097/PPO.0b013e318161d40f
Special Issue on New Drugs in the Management of Advanced Prostate Cancer: Original Articles

Despite advances in the treatment of hormone-refractory prostate cancer (HRPC) with docetaxel chemotherapy as evidenced by the TAX 327 and SWOG 99-16 trials, therapeutic options remain limited in patients with cancer that progresses while they are receiving hormone manipulation and chemotherapy. Targeted therapies against receptor tyrosine kinases of the ErbB family have shown some promise in the treatment of HRPC; however, patient characteristics defining susceptibility to ErbB-targeted therapies remain unknown in HRPC and limits their efficacy in the clinic. Targeted inhibition of downstream pathways, namely mammalian target of rapamycin (mTOR) may prove to be important in the treatment of HRPC because of the prevalence of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss, and it has been shown preclinically that mTOR inhibition reverses the phenotype of PTEN loss. Further investigation is necessary for the targeted inhibition of receptor tyrosine kinases and mTOR in HRPC. However, these classes of drugs may prove efficacious as tumoricidal agents or as chemo- and radiosensitizers.

From the Division of Medical Oncology, *Department of Medicine, and †Department of Surgery, Duke University Medical Center, Durham, NC.

Reprints: Franklin L. Chen, Duke University Medical Center, 106 Research Drive, MSRBII Box 10301, Durham, NC 27710. E-mail:

© 2008 Lippincott Williams & Wilkins, Inc.