AACR 2010: Cancer genetics: Looking back before looking forward

22 Apr 2010

Bert Vogelstein: "What we have learned from cancer genetics research should influence future cancer therapies"


In a plenary session of the AACR annual meeting in Washington, D.C., Bert Vogelstein, M.D. discussed how cancer genetics research should influence the future anti-cancer drug discovery programs.

There are more than 300 genes whose mutations play a causative role in cancer onset. They belong to the small number of core pathways through which all of these genes operate to turn normal cells into cancer cells (apoptosis, damage response, Ras etc.). These mutations are called driver mutations.

Out of these more than 90% are loss of function mutations in tumour suppressor genes, the rest (30 genes) are oncogenes. Hence, in most of the cases cancers arise as a result of factors that do not work properly (loss of function). In only a few cases is cancer actually caused by factors that are hyperactive (such as oncogenes) and therefore acted in a deregulated manner (Gain of function)

Given this, it is obvious that the mutant-protein targeted therapy cannot be the only option for identifying new drugs. That is, you cannot inhibit with a drug something that is already mutated and not functional. A valid alternative is to use the so-called mutant pathway targeted therapy. This is a cell based therapy. Examples are the PARP inhibitors and other drugs that affect the damage response or angiogenesis or metabolism.

Vogelstein says, "The single biggest challenge we face is how to apply this knowledge. We now have a mountain of information about cancer and the most difficult part is figuring out how to use this knowledge to help people."

Vogelstein was very clear about one research direction that he believes is currently underestimated but critical for overcoming this challenge: "I believe that the primary way in which cancer deaths will be reduced in the future is through early detection and prevention rather than through the cure of advanced disease."