why targetting just one oncogene may fail

[gdpawel]

It may be very important to zero in on different genes and proteins. However, when actually taking the "targeted" drugs, do the drugs even enter the cancer cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate? In other words, will it work for every patient?

What needs to be done is to sort out what's the best profile in terms of which patients benefit from this drug or that drug. Can they be combined? What's the proper way to work with all the new drugs? If a drug works extremely well for a certain percentage of cancer patients, can they be identified? If one drug or another is working for some patients (not average populations) then obviously there are others out there who would also benefit.

What's good for the group (population) may not be good for the individual, affirms that in the tactic of using "fresh" biopsied cells to predict which cancer treatments will work best for the individual patient, these "smart" drugs have to get inside the cells in order to "target" anything.

So all the validation of this gene or that protein providing us with a variety of sophisticated techniques to provide new insights into the tumorigenic process, if the targeted drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, it just isn't going to work. Each targeted drug is not for everybody. Even when the disease is the same type, different patients' tumors respond differently to the same agent or agents.

Once we are able to take a cancer specimen, analyze it, and follow those genetic changes that influence particular pathways, then one, two, three or more targeted therapies, perhaps simultaneously, will be able to completely interrupt the flow of the cancer process.

It's not a case of throwing targeted drugs at the problem. It's knowing "what" targeted drugs work and "how" to use them in "individual" patients (not average populations). The problem is that few drugs work the way scientists think they do and few of them take the time to think through what it is they are using them for.

The headlong rush to develop tests to identify molecular predisposing mechanisms still does not guarantee that a drug will be effective for an individual patient. Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class.

Upgrading clinical therapy by using drug sensitivity assays measuring "cell death" of three dimensional microclusters of live "fresh" tumor cells, can improve the situation by allowing more drugs to be considered. The more drug types there are in the selective arsenal, the more likely the system is to prove beneficial.

http://weisenthalcancer.com/

http://www.rational-t.com/