There are hundreds of thousands of mutation combinations that lead to cancer. This is why it is such a difficult problem.

Has anyone done a proof of principle though. You only need to test one of the combinations. I don't think anyone has been able to do this.

This is a good question for which I don’t have the answer. We know from epidemiological research that you need at least 5 independent mutations to get to metastatic cancer. With the new CRISPR technology it should now be possible to make cells containing just 5 mutations which should then be able to be studied.

The bigger problem is these 5 mutations can be drawn from hundreds of possible genes so the combinations are almost endless.

>"We know from epidemiological research that you need at least 5 independent mutations to get to metastatic cancer."

This is all based on the Armitage and Doll 1954 theory, they write: "This result will be valid for large values of t (of the order of a human lifetime) provided that p_l x t, P_2 x t, ..., p_r x t are all sufficiently small (as could be assumed in an application of this theory to human cancer)" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2007940/

Here, the "the probability of occurrence of the r-th change, in that line of descent, is p, per unit time [t]". So obviously if p or t is large enough, the probability of dying from cancer goes above 1, which is non-physical. There is a simplification being made here that was reasonable in the pre-computer age. What happens if you implement the same theory without that simplification?