Overcoming cunning cancer cells

02 December 2012
Posted by Kat Arney.

Drug resistance is a major problem when it comes to treating cancer - in many cases, chemotherapy drugs work in the short term, but the tumours become resistant to treatment and keep growing. This is not only true for older drugs but for newer targeted therapies too, and it happens because cancer cells evolve to overcome the effects of the medication. There's a lot of research going on around the world aimed at understanding and overcoming this resistance and now a team of European and US researchers, led by Rene Bernards at the Netherlands Cancer Institute, have identified an entirely new mechanism by which cancer cells can develop drug resistance. They've just published their results in the journal Cell. Small cell lung cancerThe researchers started by looking at lung cancer cells carrying a specific genetic fault - a fusion between two genes called EML4 and ALK, which drives them to grow. They then used a technique called RNA interference, testing 24,000 tiny fragments of RNA in these cells which switch off 8,000 different genes, one at a time, in cancer cells that have been treated with different drugs. They were searching for cells that had become resistant to the drug treatment, then worked out which gene much have been switched off for that to happen. And they found one - a gene called MED12 - which was rather unexpected. MED12 is part of something called the Mediator complex, which helps cells to switch genes on and off. The researchers discovered that switching off MED12 leads to the activation of a pathway called TGF-beta signalling, a kind of molecular escape route that keeps cancer cells growing out of control, even when they've been treated with drugs. The exciting thing is that are drugs that block TGF-beta signalling already in development, so maybe combining them with chemotherapy or targeted cancer treatments could help to tackle drug resistance and make the therapy more effective.

There's still a lot more to figure out about what's going on here, and this is just work on cells growing in the lab and doesn't take into account all the complicated interactions between cancer cells and the tissue around them, which we know are important in helping tumours deveop drug resistance. So it's still a long way from being something that could be turned into immediate benefits for cancer patients. But it's certainly a significant and exciting finding that takes us a big step closer to understanding how cancers become resistant to therapy, and how it might be possible to overcome it.

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