Drug Development for Molecular Targets in Cancer Therapy
Targeted therapies of cancers are currently under intensive development. These include both small molecule inhibitors and monoclonal antibodies, which block specific signaling molecules in oncogenic pathways. For example tamoxifen and other drugs target estrogen receptor, aromatase, androgen receptor, and the epidermal growth factor receptor (EGFR) family that has a long record in the treatment of breast cancers. Drugs can be also targeted to proteins involved with the survival and function of tumor associated stromal, endothelial, as well as circulating cells recruited to cancer sites, e.g. VEGF, FGF, and nuclear factor (NF)kappaB. A major obstacle in cancer therapy is drug resistance that underlies tumor recurrence. Recently, a direct link between the epithelial-mesenchymal transition (EMT) process and increased drug resistance has been demonstrated in cancer cells in vitro. Indeed, EMT represents a profound change in cell phenotype, causing immotile epithelial cells to acquire features such as motility, invasiveness, and resistance to apoptosis. In addition, it is well accepted that EMT results in many attributes of normal and cancer stem cells. Understanding the molecular mechanisms of EMT could open new avenues on many fronts for effective cancer therapy.