Genetic (Personalized) Medicine: EGFR Mutation Predicts Response to Lung Cancer Therapy.

[NNadir]

It happens that all human beings are genetically modified mutants, and, it shouldn't come as a surprise - but somehow does - that Monsanto corporation had nothing to do with it. Gene insertion is a regular feature observed in all living things, nowhere better evinced than by the human genome project which showed that a huge percentage of human DNA is, in fact, viral in origin.

Of course, even genes that historically had nothing to do with viruses - if such DNA in fact exists - changes over time, mutates. In fact sequences that are highly conserved in genetics across species (and therefore across evolutionary time) - superoxide dismutase is one that comes to mind - are rare compared with sequences that are highly variable. It is well known that many functional proteins have mutated so dramatically as to have evolved entirely different functionalities.

Not all mutations are necessarily disavantageous, no matter what they wanted to tell you in 1950's science fiction movies. For instance the rare dominant six fingered gene that is known to occur among certain Celtic populations, particularly in Scotland, might represent a real benefit to piano players and guitar players, for instance, and, should natural selection for some reason confer a survival advantage to piano players who can manage chords other folks can't, actually become essential to survival.

I recently had a discussion over in the lounge on the genetic basis of a response to hypertension medications, including the drug omipatratilat that was ruled non-approvable by the FDA even though it may have incurred survival benefits to one population while putting risks before another genetic population.

Here's another interesting case. Survival rates in response to chemotherapy treatment with some cancer treatments have, according to a report released at the American Society of Clinical Oncologists, have been shown to have a genetic basis. In particular, mutants having a mutation in the EGFR protein's codons, have a superior response to gefitinib, a first line treatment for non-small cell lung cancer. To wit:

TORONTO, May 20 -- Mutation analysis predicted response to different therapies in a randomized clinical trial that compared two first-line regimens for non-small cell lung cancer (NSCLC).
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Patients with epidermal growth factor receptor (EGFR) mutations had significantly better progression-free survival (PFS) and overall response rate when treated with gefitinib (Iressa), Masahiro Fukuoka, M.D., told the media before the American Society of Clinical Oncology meeting.

In contrast, patients who tested negative for EGFR mutations fared better with carboplatin-paclitaxel chemotherapy.

"EGFR mutation was a strong predictive biomarker for a differential progression-free survival and overall response rate with gefitinib versus carboplatin-paclitaxel in this clinically selected first-line setting, indicating that a molecularly defined population will benefit most from first-line gefitinib," said Dr. Fukuoka, of Kinki University School of Medicine in Osaka, Japan.

In response to a question, Dr. Fukuoka said absence of EGFR mutations identified a subgroup of patients who would be more likely to respond to conventional chemotherapy...

http://www.medpagetoday.com/MeetingCoverage/ASCO/14297">ASCO: Mutation Analysis Predicts Response to Lung Cancer Therapy.

I am not a clinical oncologist, but I attended an ASCO meeting a few years back in another context and found it fascinating. I wrote about it on another website where I used to write:

http://www.dailykos.com/storyonly/2008/6/2/192053/4644">I Took Some Time To Indulge My Personal Interest in Brain Cancer Today.