Signal Transduction Inhibitors in the Treatment of Breast Cancer

Current systemic therapies for breast cancer are often limited by their non-specific mechanism of action, unwanted toxicities on normal tissues and short-term efficacy due to the emergence of drug resistance. Identification of the molecular alterations in key proteins involved in breast cancer cell proliferation and survival resulted in development of various signal transduction inhibitors as new treatment strategy. Preclinical data support the use of these agents in breast cancer, including estrogen receptor positive breast cancer patients in which signalling inhibitors might prevent or treat resistance to endocrine therapy. These compounds have generally shown an acceptable toxicity profile. However, little clinical activity of signalling inhibitors as monotherapy in breast cancer patients has been reported up to now. Furthermore, the preliminary results of clinical trials of combinations of signalling inhibitors and endocrine therapies published to day are rather disappointing. These negative findings are likely due to the occurrence of mechanisms of resistance to these drugs.