Patient’s DNA May Be Signal to Tailor Medication

I'm not at all sure how 50% of a large group can be accurately described as a "fortunate few."

I also think the author missed the fact that most of the physicians I encounter switch meds if the patient isn't responding as expected. Not to mention the non-compliance rate, which if not correctly accounted for skews results--no med is effective if it's not taken.

As we find better ways of tracking effectiveness, and then predicting it, by all means take advantage of that ability.

Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes.

Targeted therapies are typically not very effective when used singularly or even in combination with conventional chemotherapies. The targets of many of these drugs are so narrow that cancer cells are likely to eventually find ways to bypass them.

Physicians may have to combine several targeted treatments to try an achieve cures or durable responses for more complicated tumors like those that occur in the breast, colon and lung.

These targeted therapies produce limited results because they can help a relatively small subgroup of cancer patients. With targeted therapy, the trick is figuring out which patients will respond. Tests to pinpoint those patients cannot be accomplished with genetic testing.

The challenge is to figure out which patients to give these drugs to. There are supposed to be targeted molecular assays to match targeted cancer therapies to those cancer patients.

However, all the gene amplificaton studies can tell us is whether or not the cancer cells are potentially susceptible to a mechanism/pathway of attack. They don't tell you if one drug or combination is better or worse than some other drug or combination which may target a certain mechanims/pathway.

The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems’ response to drug treatments, not just one target or pathway, or even a few targets/pathways.

No gene-based test can discriminate differing levels of anti-tumor activity occurring among different targeted therapy drugs. Nor can an available gene-based test identify situations in which it is advantageous to combine a targeted drug with other types of conventional cancer drugs.

If you find one or more implicated genes in a patient's tumor cells, how do you know if they are functional (i.e. 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.

All cells exist in a state of dynamic tension in which several internal and external forces work with and against each other. Just detecting an amplified or deleted gene won't tell you anything about protein interactions.

Are you sure that you've identified every single gene that might influence sensitivity or resistance to a certain class of drug? Assuming you resolve all of the preceeding issues, you'll never be able to distinguish between susceptibility of the cell to different drugs in the same class. Nor can you tell anything about susceptibility to drug combinations.

And what external facts such as drug uptake into the cell? Gene profiling tests for individual patients are performed on dead, preserved cells that are never actually exposed to the chemotherapy drugs whose activity you're trying to assess.

Assessing gene expression is important in order to identify new therapeutic targets and thereby to develop useful new drugs. However, it is still years away from working successfully in predicting treatment response for individual patients and it will never, for very practical reasons be as effective as the cell culture method, which exists today and is not hampered by the problems associated with gene expression tests.