Monday, June 1, 2009

From Targeted Cancer Drugs to Targeted Cocktails

A partnership between Merck and AstraZeneca is a sign that the era of targeted cancer drugs is maturing.
Posted by at

1 comment:

Greg Pawelski said...

Just identifying molecular predisposing mechanisms still does not guarantee that a drug will be effective for an individual patient. Nor can it, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class.

The challenge is to identify which patients targeted treatment will be most effective. Tumors can become resistant to a targeted treatment, or the drug no longer works, even if it has previously been effective in shrinking a tumor. Drugs are combined with existing ones to target the tumor more effectively. Most cancers cannot be effectively treated with targeted drugs alone.

Molecular testing methods detect the presence or absence of selected gene or protein mutations which theoretically correlate with single agent drug activity. Cells are never exposed to anti-cancer agents.

What is needed is to measure the net effect of all processes within the cancer, acting with and against each other in real time, and test living cells (not cell lines) actually exposed to drugs and drug combinations of interest. The key to understanding the genome is understanding how cells work. How is the cell being killed regardless of the mechanism?

Functional profiling assess the net effect of all inter-cellular and intra-cellular processes occurring in real time when cells are exposed to anti-cancer agents (targeted or conventional). Tests are performed using intact, living cancer cells plated in 3D microclusters. It allows for testing of different drugs within the same class and drug combinations to detect drug synergy and drug antagonism.

The core understanding is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a targeted drug could perturb any of these pathways, it is important to examine the effects of drug combinations within the context of the cell.

Both genomics and proteomics can identify potential therapeutic targets, but these targets require the determination of cellular endpoints. You still need to measure the net effect of all processes, not just the individual molecular targets.

June 1, 2009 at 6:57 PM

Post a Comment

Subscribe to: Post Comments (Atom)