20.19: Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific molecular targets to treat different kinds of cancers.
Angiogenesis plays a huge role in the tumor microenvironment by providing necessary oxygen and nutrients to the growing tumor cells. Therefore, the use of specific inhibitors, such as bevacizumab that can bind circulating vascular endothelial growth factors and block the formation of new blood vessels, can help to restrict the growth of tumor cells.
Another commonly used strategy against cancer is the use of monoclonal antibodies, such as alemtuzumab, trastuzumab, and cetuximab, that can directly target tumor cells. While some of these antibodies target a specific marker on the cancer cells, others just improve the immune response in the body.
The ubiquitin-proteasome pathway plays a crucial role in apoptosis, cell survival, cell-cycle progression, DNA repair, and antigen presentation in eukaryotic cells. Inhibitors of this pathway, such as bortezomib, carfilzomib, and ixazomib, are successfully used to treat myeloma and mantle-cell lymphoma (MCL).
Signal transduction inhibitors
Most cancer cells have abnormal signal transduction pathways that lead to their uncontrolled cell growth, proliferation, and survival. The development of drugs that can inhibit the aberrant signal transduction elements in the cancer cells, such as the surface receptors or the downstream effectors, such as kinases, is a promising avenue for targeted therapy. For example, epidermal growth factor receptor or EGFR is a transmembrane receptor tyrosine kinase that is abnormally expressed in some cases of cancer. Gefitinib, an FDA-approved drug, is a EGFR inhibitor that is successfully used for the treatment of non-small cell lung cancer.