PI3 kinase activation and response to Trastuzumab Therapy: what's neu with herceptin resistance?
Trastuzumab is an established therapy for women with breast cancers that overexpress HER2. Despite its proven benefit in treating breast cancer, not all women derive benefit from this monoclonal antibody, and resistant disease can develop. In this issue of Cancer Cell, Berns et al. present evidence that activation of the PI3 kinase pathway, either via loss of the tumor suppressor PTEN or through oncogenic stimulation of PIK3CA, can mediate trastuzumab resistance. This study extends important work of others and forms the rationale for future investigations combining inhibitors of the PI3 kinase pathway in conjunction with trastuzumab therapy.
Park
Ben Ho
BH
Breast Cancer Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Baltimore, MD 21231, USA.
Davidson
Nancy E
NE
D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D058534:Class I Phosphatidylinositol 3-Kinases; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D018579:Patient Selection; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human