[Dean's World] Dave Schuler: CancerGate

[notify at powerblogs.com]

Posted by Dave Schuler:
CancerGate
http://www.deanesmay.com/posts/1186357347.shtml


   by George L Gabor Miklos, PhD and Phillip John Baird, MD PhD

    Finding all the mutations in all cancers

   The director of the National Institutes of Health, Elias Zerhouni,
   approved major funding for a pilot project to find all the mutations
   in certain cancers. As reported in the New York Times in 2005, this
   search would be expanded into a $12 billion megaproject if it were to
   show signs of success (85). In June of 2007, however, it was revealed
   that fifty percent of the particular brain samples to be used for this
   study are unusable. This is due to the discovery of large amounts of
   dead (necrotic) tissue in the samples (86). Any competent pathologist
   would have pointed out this problem before the start of the project,
   since large amounts of necrotic tissue are a well-known hallmark of
   this particular brain cancer, termed glioblastoma multiforme. For the
   megaproject proponents to somehow stumble upon this basic realization,
   after more than two years, is nothing short of a scandal. In
   scrambling to limit the fallout from this deficiency in planning, the
   NCI is now allocating more funds to determine the best practices to
   use in tissue sample preservation (86).

    The fatal flaw

   There is an even bigger problem with the mutational basis of the
   megaproject. Most of the hundreds of so called âcancerâ genes that
   have already been prioritized to date have been designated as such on
   the basis of statistical attributes, not on their clinical
   significance (6). Reanalysis of these much-touted data on newly found
   âcancerâ genes (6) has now shown that few if any of these genes are in
   fact significant (7). There is no proper statistical basis for their
   elevation to âcancerâ gene status. <

    Cancer genes

   The public is lead to believe by prominent cancer researchers and the
   media that every important âcancerâ gene is in the process of being
   tracked down by applications of new sophisticated technologies. The
   promise is that once all âcancerâ genes have been cataloged, it will
   be clear where the drug targets will be found. However, the criterion
   being used for a âcancerâ gene is simply that it carries a mutation in
   some tumors. Thus a particular gene which was found to be mutated in
   only 1 out of 61 lung cancer patients is still considered to be a
   âcancerâ gene (61). Another gene, mutated in 74 out of 199 colorectal
   cancers, 1 out of 24 lung cancers, none out of 11 pancreatic cancers
   and none out of 12 brain cancers, is nevertheless classified as a
   âcancerâ gene (61). The âcancerâ gene proponents seem unable to
   comprehend that such weak correlations are not indicative of
   causation.

   More recently, analysis of over 500 genes considered to be potentially
   critical in causing cancer, were tested for the presence of mutations
   in each of them in over 200 different tumors.

   Nearly 40% of the histologically documented tumor samples from
   patients had no mutations whatsoever in these supposedly important
   âcancerâ genes(32).

   The party line on such data is straightforward. As long as a
   particular gene is mutated in some cancers, it is considered to be a
   âcancerâ gene, even though the data fail to satisfy even the minimum
   scientific standards for causality (61). When the standards have
   fallen this low, then we are no longer in the realm of world class
   research but in the realm of voodoo genes and scientific spin. It is
   nothing short of a disgrace.

    The Delusionists and the Spin Doctors

   There is now an overwhelming amount of clinical and drug resistance
   data pointing to the ill-conceived nature of the mutational
   megaproject and for the lack of a causative role of hundreds of
   âcancerâ genes. The spin doctors are nevertheless busy, arguing that
   if you turn over every rock, there is a lot more to be found (87).
   Indeed there is. However, the reality is that most of what is found
   has no clinical relevance whatsoever. What we are witnessing is third
   rate science. It is indicative of stale and unimaginative leadership
   (54,87-91).

   The mutational delusionists doggedly continue to examine the minutiae
   of the wounded (the millions of mutations in primary tumors), hoping
   to learn what is going wrong (6,32,51,54,87-94). They fail to face the
   one important issue in the War on Cancer, are mutations the main
   enemy? As the clinical data on BRCA1 and BRCA2 have revealed so
   clearly, mutations are not the main drivers of cancer. The focus needs
   to be on clinically relevant entities that bear on the survival of the
   patient, namely the massively altered DNA contents in metastatic cells
   that play a pivotal role in drug resistance and survival.

    The clinical deliverables: patients are still waitingâ¦and waitingâ¦and
    waiting

   The above findings expose the contrasts among the absolute necessity
   for careful examination of tumor tissues, the statistical pitfalls
   inherent in data analyses and the importance of generating data that
   relate to the survival of the patient. Unless First Class standards
   are soon reinstated, there will be no clinical deliverables. As
   pointed out recently in Newsweek by Sharon Begley, This is no way to
   cure cancer(95).

   The realism is that there is currently no magic bullet that targets a
   specific solid cancer for reasons that should now be apparent (47,48).
   It is massive DNA alterations that drive cancer
   931,45-48,52,53,61,65,73-76,80). Thus if drugs are currently still the
   only immediate source of therapies, then they need to be applied in
   innovative ways to metastatic growths (96,97).

   It is paradoxical that American medical technology is outstanding,
   that American doctors are better paid than anywhere else in the world
   and yet vacuous cancer enterprises of marginal clinical value are so
   strongly supported by American institutions.

   The National Cancer Institute has an annual $5 billion budget and a
   unique track record. It has consistently delivered one product year
   after year; unfulfilled promises of cancer cures (theyâre still just
   around the corner). Are patients and doctors still unable to see that
   the current approach, namely; more money, more technology and more
   stratospheric hype, is not leading to cures?