Targeted Cancer Therapies

Traditional cancer therapies, such as chemotherapy and radiotherapy, are not highly selective in targeting cancer cells and, therefore, have various side effects on normal cells of the body as well. 

In contrast, targeted cancer therapies use drugs designed to target specific molecular structures that are present only in the cancer cells, and are absent in normal cells.

For example, healthy cells have two separate genes, BCR and ABL1. In chronic myeloid leukemia, chromosomal translocation fuses a part of the BCR gene with the ABL1 gene, leading to the synthesis of fusion protein BCR/ABL1.

This abnormal fusion protein drives uncontrolled cell proliferation and results in an excessive number of white blood cells in the bloodstream.

Imatinib mesylate is a small molecule kinase inhibitor that can specifically target the BCR/ABL1 fusion protein, preventing its activity and the downstream signaling pathways that control cell proliferation.

The drug also inhibits the ABL1 protein in the healthy cells, but additional redundant tyrosine kinases in such cells cover up for the loss of function of the ABL protein.

Imatinib mesylate is an example of a successful targeted molecular therapy against cancer with a response rate as high as 90%. 

Targeted therapy is also used in some cases of breast and ovarian cancer that have inactive tumor suppressor genes, BRCA1 and BRCA2.

Cancer cells with inactive BRCA1 and BRCA2 proteins rely on poly (ADP-ribose) polymerase or PARP enzyme for DNA repair and survival.

This means that drugs which can selectively inhibit PARP enzyme activity can permanently block DNA repair in BRCA1 and BRCA2 deficient cancer cells. In contrast, healthy cells remain unaffected because of the active BRCA1 and BRCA2 DNA repair pathway.

Monoclonal antibodies directed against tumor-specific proteins can also be used for targeted therapy. For example, the trastuzumab antibody is used to inhibit the activity of overexpressing human epidermal growth factor receptor two or HER2, a receptor tyrosine kinase protein in some breast cancer patients.

However, since normal cells also express HER2 protein, HER2 targeted therapy can also affect normal cells and cause side effects.