The universe of normal and cancer cell line responses to anticancer treatment: Lessons for cancer therapy

Abstract

According to the Surveillance Epidemiology and End Results report, 1,479,350 men and women will be diagnosed with and 562,340 will die of cancer of all sites in 2009, indicating that about 40% of the cancer patients do not respond well to current anticancer therapies. Using tumor and normal tissue cell lines as a model, we show this high mortality rate is rooted in inherent features of anticancer treatments. We obtain that, while on average anticancer treatments exhibit a two fold higher efficacy when applied to cancer cells, the response distribution of cancer and normal cells significantly overlap. Focusing on specific treatments, we provide evidence indicating that the therapeutic index is proportional to the fraction of cancer cell lines manifesting significantly good responses, and propose the latter as a quantity to identify compounds with best potential for anticancer therapy. We conclude that there is no single treatment targeting all cancer cell lines at a non-toxic dose. However, there are effective treatments for specific cancer cell lines, which, when used in a personalized manner or applied in combination, can target all cancer cell lines.