Cdc42: an effector and regulator of ErbB1 as a strategic target in breast cancer therapy

ErbB1 and ErbB2 are often overexpressed in breast cancer. Overexpression of these receptors is correlated with poor prognosis. ErbB receptor-targeted therapies have been developed for the treatment of human breast cancer. While ErbB2 overexpression is usually caused by gene amplification, the mechanism for ErbB1 overexpression remains elusive. An important mechanism for the downregulation of ErbB1 is via Cbl-mediated receptor ubiquitination and degradation. Increasing evidence suggests that loss of Cbl-regulated ErbB1 degradation contributes to ErbB1 overexpression in cancer cells. Cdc42 is overexpressed in some breast cancers and evidence is accumulating that activated Cdc42 contributes to the accumulation of ErbB1 in cells through the regulation of c-Cbl function. Different therapeutic strategies targeting ErbB receptors and Cdc42 will be reviewed and discussed.