RB in breast cancer: at the crossroads of tumorigenesis and treatment.
Cancer is a highly heterogeneous disease, wherein specific determinants modulate disease severity and therapeutic outcomes. In breast cancer, significant effort has been channeled into defining critical genetic effectors of disease behavior. One key molecular determinant is the retinoblastoma tumor suppressor (RB), which is functionally inactivated in the majority of human cancers, and aberrant in nearly half of breast cancers. Deficiency in RB function compromises cell cycle checkpoints, contributes to aggressive tumor proliferation, and is associated with advanced disease. Recent investigation indicates that RB-deficiency has dramatic and disparate effects on the response to therapeutic modalities utilized in the treatment of breast cancer. Loss of RB function promotes inappropriate cell cycle progression during therapeutic challenge. In the context of cytotoxic therapies, this lack of checkpoint function leads to increased sensitivity to the agent. However, RB-deficiency efficiently bypasses the anti-mitogenic function of hormonal therapies and is associated with early disease recurrence following tamoxifen therapy. Thus, RB-pathway status has powerful effects on both tumorigenic proliferation and therapeutic response, and may represent a critical basis for informing breast cancer therapy.
Bosco
Emily E
EE
Department of Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA.
Knudsen
Erik S
ES
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D000970:Antineoplastic Agents; D016160:Retinoblastoma Protein