Improving cancer therapies by exploiting drug resistance in cancer

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fairly difficult
News-Medical talks to Professor David Thomas about his recent research identifying the mechanisms behind cancer cells developing resistance to drugs.
Thought Leaders Professor David Thomas Head of the Cancer Theme Garvan Institute of Medical Research

News-Medical talks to Professor David Thomas about his recent research identifying the mechanisms behind cancer cells developing resistance to drugs and how this new understanding could be used to pioneer better cancer therapies.

What led you to carry out this research?

The first reason is that we were very interested in thinking about drug resistance in a different way. Drug resistance is arguably the most significant challenge to cancer drug development at present. Most of the drugs that we have spent billions of dollars developing, and pay billions of dollars to provide to patients, are used in patients who are incurable, and they eventually fail.

In terms of thinking laterally about how to have an impact, it seems important to ask: what can we learn about why cancer drugs fail?

The second thing is that we were not after the relatively specific problem of how any individual drug fails. There has been a lot of research studying why, for example, drugs that target the epidermal growth factor receptor stop working because of the acquisition of a specific mutation that is resistant to the drug to which the patient was originally exposed.

That is not so much how resistance arises in each case, but the general mechanisms--if any--which increase the probability of resistance. We were more interested in whether there was a fundamental process across many drugs and applicable across many cancers which might drive the emergence of those specific resistance mutations.

A final reason is due to my thoughts back in 2001, a long time ago. The reason I wondered about this process of stress-induced mutagenesis was because I am a fundamental believer in the principles of Darwin, of natural selection, and that genetic diversity fundamentally drives evolution.

The theory was that the mutation process itself was largely passive and random, and it was the environment that…
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