Today I went to a lecture by Nick Cross on tyrosine kinase inhibitors in chronic leukemias. The lecture was a tour-de-force, but I came away profoundly depressed. Nick runs an excellent genetics unit and is extremely erudite. He has managed to identify 43 chromosomal translocations in the chronic leukemias in which conjoined genes result in a constitutively activated tyrosine kinase that has the effect of causing the leukemic cell to continue to divide even when it is not receiving an appropriate signal from its environment.
This has nothing to do with CLL, by the way, the pardigmic disease is chronic myeloid leukemia in which the BCR/ABL tyrosine kinase is always in the switched on mode. Nick has looked at a variety of atypical chronic myeloid leukemias and has sorted out the molecular mechanisms.
Excellent though the science was there were several depressing features. First, in one case they had identified a Gleevec-like inhibitor which switched the tyrosine kinase off and would have had the effect of controling the leukemia, but so few patients suffered from this particular variant that no pharmaceutical company would spend the money to manufacture the product. Second, although he had identified 43 molecular mechanisms these represented less than 10% of all cases of atypical chronic myeloid leukemia. This is a rare variant of a rare disease; there are only 750 new cases of chronic myeloid leukemia in the UK every year.
The chronic myeloproliferative diseases are single gene disorders - there is usually only one molecular mistake. The common cancers, on the other hand, have 6, 7 or 8 molecular mistakes. If single gene diseases are so complex, how much more complex must the common cancers be?
When Gleevec was discovered I was very excited. The age of molecular therapies was dawning. That was 9 years ago. All we have done since then is produce one failed drug - Iressa - for common cancers. It is still the case that the most effective treatment for cancer is surgery, a treatment 150 years old.
The third depressing feature came from a meeting I went to the day before. WE were proposing a trial of mini-dose Revlimid for maintenance therapy in CLL. This was being opposed on the grounds that as the drug was so expensive, no matter how effective it might be, it would never pass NICE, and therefore there was no point in doing the trial. If Revlimid (a relatively easy to make molecule) is too expensive, what hope is there for new drugs in cancer.
The fourth thing that depressed me was seeing a doctor smoking. I have always refused to work on lung cancer on the grounds that the problem is already largely solved. Just stop tobacco smoking. As we unravel these molecular mechanisms at huge expense, society as a whole is unwilling to give up the thing that causes the commonest type of cancer. Why should we bother?