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Wodarz D. Use of oncolytic viruses for the eradication of drug-resistant cancer cells. J R Soc Interface. 2009 Feb 6;6(31):179-86. PMID: 18664430

Dominik Wodarz, professor of Ecology and Evolutionary Biology at UC-Irvine, writes on the theoretical possibility of some day using oncolytic viruses to eradicate drug-resistant cancer cells prior to treatment with targeted therapies such as imatinib. Although critical conditions necessary for experimental investigation have yet to be reached, Wodarz hopes the study will stimulate new avenues of research and thinking.

Wodarz developed his mathematical model working from a concept in population dynamics, apparent competition: 

“Even if two populations or two species do not directly compete with each other, the fitter species can drive the less fit species extinct if they are infected by the same pathogen. For example, if the growth rate of the drug-sensitive cancer cells is higher than that of the resistant cancer cells, then the resistant cells will be driven extinct if a virus can infect both cell populations. In the context of CML [chronic myeloid leukemia] therapy with the targeted drug imatinib, it has been reported that certain drug-resistant mutants have a reduced growth rate and are less fit than the drug-sensitive cells."

According to the model, when drug-resistance mutations are demonstrated to have a "fitness cost" compared with drug-sensitive cells in a cancer, a virus can be used to drive resistant cell clones toward extinction prior to drug therapy. Because both drug-resistant and drug-sensitive cancer cells share the virus, competition with the fitter drug-sensitive cells would drive the resistant cells extinct. Then drugs could be used to treat the cancer without the emergence of resistance. 

Currently no cancers meet the three conditions that must exist before the model can be tested: the existence of an efficient targeted drug therapy, a detailed knowledge of drug resistance mutations, and a feasible oncolytic virus.

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