Successful targeting of ErbB2 receptors-is PTEN the key?
Women with ErbB2-positive breast cancer have a poor prognosis, and frequently, chemotherapy treatment is ineffective. The ErbB2-targeted antibody trastuzumab improves survival when given with chemotherapy to patients with ErbB2-overexpressing metastatic disease, but treatment is not curative, and primary resistance is common. Postulated mechanisms of action for trastuzumab include immune-mediated cytotoxicity and receptor downmodulation. A study in this issue of Cancer Cell suggests that trastuzumab causes rapid activation of the PTEN lipid phosphatase, which in turn downregulates the phosphatidylinositol 3'-kinase (PI3K) pathway. Resistance to trastuzumab occurs when PTEN function is lost, suggesting that PTEN activation is a critical component of the therapeutic effect.
Crowder
Robert J
RJ
Department of Medicine, Division of Oncology, Washington University School of Medicine and Siteman Cancer Center, Campus Box 8056, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Lombardi
Donald P
DP
Ellis
Matthew J
MJ
D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000068878:Trastuzumab; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D025521:Tumor Suppressor Proteins; C494929:PTEN protein, human