| Dr Stephen Little at DxS Ltd explores a world of targeted therapeutics and companion diagnostics as a new era in cancer treatment dawns
As Francis Collins, the Director of the National Human Genome Research Institute, said at this year’s American Association for Cancer Research Meeting in Los Angeles, “Cancer is a disease of the genome.” The underlying changes responsible for the growth and development of tumours are mutations, deletions, rearrangements and other genomic alterations, which give rise to the uncontrolled cell growth at the heart of all cancers. To truly understand the basis of cancer, and thereby identify potential diagnostics and treatments, we must first understand these changes at the genetic level.
THE RISE OF TARGETED THERAPIES
The first working draft of the human genome was published in 2000 and was the culmination of 10 years’ work. Since then, technology advances have meant that the cost of genomic analysis has fallen to such an extent that it is now feasible to contemplate complete genetic analyses on individual tumours to identify all of the underlying changes. For example, a few years ago a complete genome scan on 1,000 cases and controls would have cost $10 billion – now the same information can be achieved at a cost of $800,000.
One outcome of this new-found technological power is a greater understanding of the cell growth control pathways which are disrupted in cancer, this has led to a new set of drug targets. In the past, the majority of cancer drugs were cytotoxics – compounds which were poisonous to all cells in the body and relied on the fact that the faster growing tumour cells were more susceptible to their harmful effects. Now there is a move to targeted therapies – drugs which specifically inhibit the disrupted control pathways in the cancer. Figure 1 compares cancer drugs on the market in 2001 to drugs in development in 2006.
EARLY SUCCESS
This approach is already paying off with some remarkable early achievements. Perhaps the most striking is the use of the Novartis drug Gleevec for the treatment of chronic myelogenous leukaemia (CML) and some forms of acute lymphoblastic leukaemia (ALL). CML is characterised by a specific translocation that swaps a region of chromosome 22 with a section of chromosome 9 and in doing so creates a gene fusion known as BCR-ABL. It is the action of this novel gene that drives the development of the cancer. Gleevec is designed to specifically inhibit the action of the BCRABL protein and is demonstrating excellent efficacy without the severe side effects of traditional cancer therapies.
Although CML is not a particularly common form of cancer, Gleevec is important because it illustrates the principal of targeting specific cancer pathways. No doubt encouraged by Novartis’s success, other companies have also targeted specific pathways and now there are many drugs on the market (or in development) targeting specific growth control pathways that are known to be altered during cancer development (see Table 1). |
