Ras Signaling in Breast Cancer

Abstract

Ras proteins mediate extracellular and cytoplasmic signaling networks via receptor tyrosine kinase. The Ras pathway induces activation of signaling molecules involved in cell proliferation and growth, cell survival and apoptosis, metabolism, and motility. Although Ras mutations in breast cancer are not frequently reported, hyperactivation of Ras signaling plays an important role in breast cancer growth and progression. Oncogenic Ras activation occurs via loss of Ras GTPase-activating proteins, overexpression of growth factor receptor, and stimulation by various cytokines. Effective control of oncogenic Ras is one of the therapeutic strategies in breast cancer. The mechanisms of intracellular localization, activation, and signaling pathway of Ras in cancer have been used to develop therapeutic candidates. Recent studies have reported an effective therapy for breast cancer by inhibition of enzymes involved in the posttranslational modification of Ras, such as farnesyltransferase and geranylgeranyltransferase 1, and anti-cancer therapies targeting the epidermal growth factor receptor (EGFR). Emerging targets involved in EGF-mediated Ras activity in breast cancer have shed new insight into Ras activation in breast cancer progression. These alternative mechanisms for Ras signaling pathway may suggest novel therapeutic approaches for targeting Ras in breast cancer. In spite of the difficulties in targeting Ras protein, important discoveries highlight the direct inhibition of Ras activity. Further studies may elucidate the effects of targeting Ras protein and the clinical relevance thereof.