(PARP inhibitors) Experimental cancer drugs cut tumors off from repair tools

[gdpawel]

Small molecule enzyme (PARP) inhibitors may serve as a potent approach for prevention of BRCA related breast cancer. However, the use of this strategy for therapeutic treatment for hereditary breast cancers is dependent on the continued susceptibility of BRCA mutant cells to PARP inhibitors, which may be achieved by using a combination with other agents (Int J Med Sci. 2006: 3(4): 117-123).

Although the theory behind enzyme inhibitor targeted therapy is appealing, the reality is more complex. For example, cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes.

In other words, cancer cells have "backup systems" that allow them to survive. The result is that the drug does not shrink the tumor as expected. One approach to this problem is to target multiple pathways in a cancer cell. Another challenge is to identify for which patients the targeted treatment will be effective (enzyme inhibitors, proteasome inhibitors, angiogenesis inhibitors, and monoclonal antibodies).

Recent studies on targeted therapy have shown that tumors can become resistant to a targeted treatment. This means that the drug no longer works, even if it has previously been effective in shrinking a tumor. To solve this problem, new drugs are being designed or combined with existing ones to target the tumor more effectively.

The cancer state is typically characterized by a signaling process that is unregulated and in a continuous state of activation. These drugs promise to become an essential part of the physician's armament against cancer, particlarly those cancers that have developed resistance to other forms of treatment.

However, setbacks with drugs that specifically target specific pathways, reflect a lack of validated biomarkers. What is needed is to test the concept of targeted cancer drugs with biomarkers as pharmacodynamic endpoints, and with the ability to measure multiple parameters in cellular screens now in hand using flow cytometry.