Why do Experimental Cancer Treatments Fail? - Page 2

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Apr 28, 2003

3. Cancer cure is a long-term process. Laboratory studies and clinical trials are of necessity short term, but cancer cells are notoriously effective in learning to circumvent treatment targets. Both normal as well as cancer cells have alternate metabolic pathways, so if a cancer treatment blocks a primary pathway, the cancer eventually uses an alternate pathway to serve its needs. Jain and associates reported on a physiological mechanism by which drugs that show an initial success in treating cancer may eventually fail. They found that as tumors shrink, so do the pores of the blood vessels surrounding the tumor. Since the drug must pass through these pores in order to exert their effect, larger molecule drugs in particular may become ineffective. Survival is the most obvious measure of treatment success, but initial success may only be followed by a relapse after 5 or even 10 years.

Much needs to be learned to improve the success of experimental cancer drugs. A critical aspect is a better characterization of patients enrolled in clinical trials. Patient tumors should be biopsied and characterized on the cellular and molecular levels. The expression levels of genes and metabolic defects of the cancer can be better related to the mode of action of the experimental drug.

References

1. Jain, et. al. Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. National Academy of Sciences, Vol. 95, Issue 8, pp. 4607-4612 (April 14, 1998). Harvard Medical School News Release

2. Rothenberg, M., Carbone, D., and Johnson, D. Improving the evaluation of new cancer treatments: challenges and opportunities. Nature Reviews Cancer, Vol. 3, No. 4 (April 2003).

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