Comments on: Pharmalot… Pharmalittle… Your ASCO Round-Up http://www.pharmalot.com/2008/05/pharmalot-pharmalittle-your-asco-round-up/ News, Comment and Conversation Fri, 10 Feb 2012 21:16:46 +0000 http://wordpress.org/?v=2.6.2 By: Gregory D. Pawelski http://www.pharmalot.com/2008/05/pharmalot-pharmalittle-your-asco-round-up/#comment-357341 Gregory D. Pawelski Mon, 26 May 2008 23:30:47 +0000 http://www.pharmalot.com/?p=13662#comment-357341 If one enormously expensive drug doesn’t work well for most patients, give two enormously expensive drugs. And if that doesn’t work, trial-and-error three, or four or more. If Tykerb blocks the activation of both EGFR and HER2, why give Herceptin which blocks only HER2? And when there are too many receptors, the cancer cell still continues to grow and divide. Cancer cells have many mutations in many different pathways, so even if one route or two is shut down by a targeted treatment, the cancer cell may be able to use other routes. Targeted drugs have not been accompanied by reliable, specific predictive tests allowing for rational and economical use of these drugs. Molecular diagnostics approved often have been mostly or totally ineffective at identifying clinical responders to the various therapies. If you find one or more implicated genes in a patient’s tumor cells, how do you know if they are functional (is the encoded protein actually produced?). If the protein is produced, is it functional? If the protein is functional, how is it interacting with other functional proteins in the cell? Are you sure that you’ve identified every single protein that might influence sensitivity or resistance to these drugs? If one enormously expensive drug doesn’t work well for most patients, give two enormously expensive drugs. And if that doesn’t work, trial-and-error three, or four or more. If Tykerb blocks the activation of both EGFR and HER2, why give Herceptin which blocks only HER2? And when there are too many receptors, the cancer cell still continues to grow and divide.

Cancer cells have many mutations in many different pathways, so even if one route or two is shut down by a targeted treatment, the cancer cell may be able to use other routes. Targeted drugs have not been accompanied by reliable, specific predictive tests allowing for rational and economical use of these drugs. Molecular diagnostics approved often have been mostly or totally ineffective at identifying clinical responders to the various therapies.

If you find one or more implicated genes in a patient’s tumor cells, how do you know if they are functional (is the encoded protein actually produced?). If the protein is produced, is it functional? If the protein is functional, how is it interacting with other functional proteins in the cell? Are you sure that you’ve identified every single protein that might influence sensitivity or resistance to these drugs?

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