Novel Agents on the Horizon for Cancer Therapy

Although cancer remains a devastating diagnosis, several decades of preclinical progress in cancer biology and biotechnology have recently led to successful development of several biological agents that substantially improve survival and quality of life for some patients. There is now a rich pipeline of novel anticancer agents in early phase clinical trials. The specific tumor and stromal aberrancies targeted can be conceptualized as membrane‐bound receptor kinases (HGF/c‐Met, human epidermal growth factor receptor and insulin growth factor receptor pathways), intracellular signaling kinases (Src, PI3k/Akt/mTOR, and mitogen‐activated protein kinase pathways), epigenetic abnormalities (DNA methyltransferase and histyone deacetylase), protein dynamics (heat shock protein 90, ubiquitin‐proteasome system), and tumor vasculature and microenvironment (angiogenesis, HIF, endothelium, integrins). Several technologies are available to target these abnormalities. Of these, monoclonal antibodies and small‐molecule inhibitors have been the more successful, and often complementary, approaches so far in clinical settings. The success of this target‐based cancer drug development approach is discussed with examples of recently approved agents, such as bevacizumab, erlotinib, trastuzumab, sorafenib, and bortezomib. This review also highlights the pipeline of rationally designed drugs in clinical development that have the potential to impact clinical care in the near future. CA Cancer J Clin 2009;59:111–137. © 2009 American Cancer Society, Inc.