title: Cell signaling modifiers in prostate cancer.
abstract: 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. franklin.chen@duke.edu
authors.forename: Franklin L
authors.initials: FL
authors.lastname: Chen
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000068818:Cetuximab; D018773:Genes, erbB-1 / Q000187:drug effects; D018734:Genes, erbB-2 / Q000187:drug effects; D006801:Humans; D000077341:Lapatinib; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011494:Protein Kinases / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D000077341:Lapatinib; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000068878:Trastuzumab; D000068818:Cetuximab