Cancer Drug Targets: The March of the Lemmings

Whilst at a joint meeting with the ICR Computational Biology and Chemogenomics Team, and the Blundell Bioinformatics Group at Cambridge, this article in Forbes by Bruce Booth was brought to my attention.

This article discussed the current oncology portfolios being developed by major Pharma.  Their analysis illustrates that over 20% of current clinical oncology projects are focused on just 8 targets, each of which has at least 24 projects in clinical development, and further projects in pre-clinical development.

Bruce points out several advantages to this approach, for instance that by developing smarter follow-on molecules, some of the liabilities of the earlier molecules may be diminished possibly improving patient outcomes.  Also drugs based on different chemotypes may lead to differential responses and exhibit different toxicity profiles.  However, he concludes that this focus on a limited range of targets is a waste of resources. Although pursuing established targets may reduce the biological and chemical risk during the early stages of drug development,  “ the differentiation risks skyrocket” – at later stages of development. In particular he highlights that the downstream drugs may fail at a later, more costly stage.

Whilst agreeing that theses are all excellent targets, he suggests that resource should be more focused on the preclinical stages of drug discovery, identifying and validating new cancer targets, rather than chasing incremental improvements in drugs against existing ones.



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