Pharmalot... Pharmalittle... Good Morning

Another superb reading list, Ed!

"Erbitux should be taken only by patients who have used an agency-approved test to predict whether the drug will work." Where have I read that before? Oh! Xalkori should be taken only by patients who have used an FDA-approved test to predict whether the drug will work for ALK lung cancer.

I would not want to be denied treatment with any targeted therapy because of a gene mutation or amplification study. Neither would I want to receive treatment with any targeted therapy because of a gene mutation or amplification study. Genetic testing is not a clear predictor of a benefit or a lack of benefit.

It doesn't tell you if one targeted drug or another targeted drug is worse or better than some other drug which may target a particular pathway. Genomics is far too limited in scope to encompass the vagaries and complexities of human cancer biology.

The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. To inhibit the mutant decoy receptor, you need to inhibit the domain of the driver molecule that lies within the cell, as opposed to the domain that lies outside the cell.

There have been no static genetic testing that can accurately predict markers for selecting the patients who will benefit from treatment with targeted therapies, only theoretical predisposition to drug response. It attempts to link surrogate gene expression to a theoretical potential for drug activity.

Sorry. That dog just doesn't hunt! But the FDA just gave expanded use of Erbitux. More profit for Big Pharma!

Hi About 'two Indian Pharma CEOs Detailed:' Who writes your headlines? They do know that Rawalpindi and Pakistan are actually not part of India? You cannot arbitrarily assign all jiggery-pokery to India, you know, amusing though it is. Thanks.

Greg, the way I read the Erbitux story, after long research on the KRAS mutation, is that the drug ONLY works on wild-type KRAS genes, those without any mutation. While it's not a guarantee that it will work all the time, they do know for sure that it WON'T work with any kind of mutation of KRAS. That being said, this is a "quicker, better" likely more expensive test for the KRAS gene than was available previously. But mutations above and below KRAS in the cascade can and do wreak havoc and develop other ways to continue their growth, which is why you are so right, genetic and genomic treatments are no sure thing and we develop resistance to them rapidly. Check out the NYTimes story on the lady with Sezary syndrome to read a heart-wrenching case.

Andrea. I understand. While research has revealed when a tumor has certain KRAS mutations, the "partially effective" colon cancer drug Erbitux is very "unlikely" to work, KRAS gene testing for EGFR is not a clear predictor of a lack of benefit from EGFR antagonist antibodies in colon cancer. Of course, this leaves out dozens of other drugs and a myriad of drug combinations, which may often be even more effective in this disease. It doesn't matter if there is a target molecule in the cell that the targeted drug is going after. If the 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, drug resistance is multifactorial. KRAS genes are under the direct regulation and control of genetic elements that no one has ever studied, except for cell biologists. Attempts on the part of gene profilers to characterize patients likelihoods of response based on gene mutations are not only misguided but, may actually be dishonest. As systems biologists point out, complexity is the hallmark of biological existence. Attempts to oversimplify phenomena that cannot be simplified, have lead us in the wrong direction.

Hey, Anita, that customer service rep from Verizon that kept me on hold for an hour yesterday, was that Rawalpindi or Pakistan? Doesn't matter, all you guys sound the same, trying to sound like a computer-generated Americanized voice in an indecipherable monotone.