Update on HER-kinase-directed therapy in prostate cancer.
The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases is part of a network of pathways that are involved in the development and progression of prostate cancer. HER-kinase receptors include epidermal growth factor receptor (EGFR), HER2, HER3, and HER4, which must combine as dimers to affect signaling. Different combinations of receptors produce different qualities and levels of pathway activation. Among HER-family receptors, HER2 activation is particularly important in breast cancer, as HER2 gene amplification is associated with a distinct clinical course and response to treatment with a HER2-directed therapy (trastuzumab). Although HER2 can be over-expressed in prostate cancer, there is no clinical data to support the use of trastuzumab for prostate cancer patients. Preclinical and clinical data show that the activation of the HER-kinase axis is important for the progression of prostate cancer to androgen-independent disease. Data points towards the importance of inhibiting multiple members of the HER-kinase family to achieve more complete blockade of this axis for cancers other than HER2-overexpressing breast cancer. Multiple pharmaceutical agents that block the HER-kinase axis are currently being tested for patients with prostate cancer. These include antibodies, tyrosine kinase inhibitors, and novel strategies which seek to decrease HER2 expression.
Gross
Mitchell E
ME
Louis Warschaw Prostate Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Jo
Solomon
S
Agus
David B
DB
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology; D000728:Androgens; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D002986:Clinical Trials as Topic; D019281:Dimerization; D018450:Disease Progression; D016503:Drug Delivery Systems; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000068878:Trastuzumab
D000728:Androgens; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D008024:Ligands; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C587689:ERBB4 protein, human; C485206:pertuzumab