Cell cycle checkpoints as therapeutic targets.
Most human breast tumors arise from multiple genetic changes which gradually transform differentiated and growth-limited cells into highly invasive cells that are unresponsive to growth controls. The genetic evolution of normal breast cells into cancer cells is largely determined by the fidelity of DNA replication, repair, and division. Cell cycle arrest in response to DNA damage is an important part of the mechanism used to maintain genomic integrity. The control mechanisms that restrain cell cycle transition after DNA damage are known as cell cycle checkpoints. This review will focus on cell cycle checkpoint signaling pathways commonly mutated in human breast tumors and suggest how different components of these checkpoint pathways offer the potential for chemotherapeutic intervention.
Stewart
Z A
ZA
Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Pietenpol
J A
JA
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D015195:Drug Design; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000473:pathology