Development of rationally designed, target-based agents for the treatment of advanced colorectal cancer.
Although there have been several recent additions to the conventional armamentarium used to treat patients with advanced colorectal cancer, principally as a result of the development of selective and nonselective pharmacologic agents and antibodies, the general outcome of patients with advanced disease is still poor. However, a greater understanding of cancer biology, as well as major advances in biotechnology, is beginning to identify and characterize molecular aberrations that are common in patients with colorectal cancer. These advances have resulted in the development of a wide range of rationally designed, target-based anticancer therapeutic agents, which, by virtue of their selectivity, would be expected to produce less nonspecific toxicity and therefore higher therapeutic indices compared with nonspecific cytotoxic agents. This review will discuss several novel targets and therapeutic agents, particularly those designed to interrupt aberrant signal transduction and apoptotic processes. It will also emphasize the complexity of these systems and the need to incorporate novel clinical development paradigms based on a thorough scientific understanding of these targets.
Mita
Alain C
AC
Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, 4th floor Zeller Building, 7979 Wurzbach Road, San Antonio, TX 78229, USA. amita@idd.org
Mita
Monica M
MM
Rowinsky
Eric K
EK
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases