WITH CANCER: THE KIDS AREN’T ALL RIGHT, BUT….

With Cancer: The Kids Aren’t All Right, But They
Are Better Off Than the Adults

By

Leonard Zwelling

         In
the previous blog post, I speculated that the latest fad in cancer research,
‘omic’ analysis of human tumors, is built on a concept something like intelligent
design. I believe that because the basic hypothesis genomics seeks to prove is
that detailed genetic reductionism will unmask an inherent logic to cancer that
will allow personalized treatments based on aberrant gene expression. By
contrast, I believe cancer arises from forces more like those at play in
Darwinian evolution in which genetic alterations either naturally occurring due
to the intrinsic imperfection of cell division or by mutagenic forces like
radiation or viruses create a new genotype and associated phenotype for the
environment to chew on and either spit out (apoptosis) or swallow
(carcinogenesis).

         That
cancer in most patients arises over protracted periods of time (as indicated by
its majority prevalence in the elderly) suggests that like evolution,
carcinogenesis is a slow process albeit possibly stochastic. But there are
exceptions and we in science love to study the exceptions. The exception is
pediatric cancer.

         Pediatric
cancer, particularly that occurring in patients below the age of pubescence, is
a strange bird. It’s hard to make a strong case for environmental factors and
much easier to attribute clinical cancer in a youngster as having a genetic
origin. (Could there be a better example than retinoblastoma? I think not). Why
that is so important is that pediatric cancer, far more than any malignancy in
adults, has proven to be far more amenable to therapy—much of which was devised
through empiricism. There can be no better example of the triumph of modern
oncology in the chemotherapy age than the victory over acute lymphoblastic
leukemia in children. When I was a child, this was a fatal disease, one that
took the life of the daughter of President George H. W. Bush and his wife
Barbara. Now, most ALL patients live long lives albeit ones challenged by the
rigors of survivorship. But what a problem for modern medicine to have!
Survivorship.

         Also, what I am going to propose will appear self-serving given the job of my wife,
Head of the Division of Pediatrics at Anderson, but it is what I really
believe. Rather than constantly studying the many ways we fail in the treatment
of adult disseminated cancer, why not study our success in the treatment of
pediatric cancer? And if you want to do the numbers, just consider how much
more valuable a remission is in a 5 year old who goes on to be cured and lead a
productive, tax paying life than the same result in a 65 year old woman with
breast cancer.

         Why
do we insist on studying our failures? What about the successes of ALL, Burkitt’s
Lymphoma, Wilm’s tumor, Ewing’s sarcoma, osteogenic sarcoma and
rhabdomyosarcoma? Sure not every single patient with one of these malignancies is
cured, but a much higher percentage are than similarly staged adult cancer
patients.

         Isn’t
it possible that understanding the nature of the success in the treatment of
cancers with less of a chance of having an environmental origin, not to mention
the abundance of non-epithelial malignancies in kids, that we might actually
grasp the etiology of carcinogenesis and how the magic poisons lead to cure?
Isn’t it likely that the drugs kill tumors, and allow natural immunity, clearly
dormant when a cancer grows, to re-establish homeostasis in the organism? Could
the microenvironment of a pediatric cancer be different than that of the more typical
epithelial cancers in adults and in understanding that difference could we
render the microenvironment of an adult cancer more like that of a cancer in a
child and create a more treatable disease in the adult?

         I
need not go on.

         Most
of you will have even better ideas than these, but perhaps when we seek our
next crew of astronauts for a new moon shot, we should go for those who are
underage.

         Pediatric
cancer gets a mere fraction of the research money allocated by the NCI. There
is a single cooperative group studying these patients and doing it very poorly
as far as I can tell in that the group excludes some of the major academic
centers from its roster of phase 1 study sites.

         How
about a new initiative at the NCI or maybe at CPRIT to study the success of the
treatment of pediatric cancer instead of the failure of the treatment of adult
malignancy? To get to the moon the United States had to perfect the rocket
system that might work not the many that clearly did not. How about that model
for cancer? Instead of chronicling the numerous ways to unsuccessfully address
the lung cancer problem, how about figuring out how a formerly lethal disease
like osteosarcoma became curable in over two-thirds of the youngsters who
contract the disease?

         The
answer we are looking for may be right in front of us. Just shorter.

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