Wed, Jan 9 2013

http://www.reuters.com/article/2013/...cancer-watson-
idUSBRE90805N20130109

NEW YORK (Reuters) - A day after an exhaustive national report on cancer
found the United States is making only slow progress against the disease,
one of the country's most iconic - and iconoclastic - scientists weighed
in on "the war against cancer." And he does not like what he sees.

James Watson, co-discoverer of the double helix structure of DNA, lit
into targets large and small. On government officials who oversee cancer
research, he wrote in a paper published on Tuesday in the journal Open
Biology, "We now have no general of influence, much less power ...
leading our country's War on Cancer."

On the $100 million U.S. project to determine the DNA changes that drive
nine forms of cancer: It is "not likely to produce the truly breakthrough
drugs that we now so desperately need," Watson argued. On the idea that
antioxidants such as those in colorful berries fight cancer: "The time
has come to seriously ask whether antioxidant use much more likely causes
than prevents cancer."

That Watson's impassioned plea came on the heels of the annual cancer
report was coincidental. He worked on the paper for months, and it
represents the culmination of decades of thinking about the subject.
Watson, 84, taught a course on cancer at Harvard University in 1959,
three years before he shared the Nobel Prize in medicine for his role in
discovering the double helix, which opened the door to understanding the
role of genetics in disease.

Other cancer luminaries gave Watson's paper mixed reviews.

"There are a lot of interesting ideas in it, some of them sustainable by
existing evidence, others that simply conflict with well-documented
findings," said one eminent cancer biologist who asked not to be
identified so as not to offend Watson. "As is often the case, he's
stirring the pot, most likely in a very productive way."

There is wide agreement, however, that current approaches are not
yielding the progress they promised. Much of the decline in cancer
mortality in the United States, for instance, reflects the fact that
fewer people are smoking, not the benefits of clever new therapies.


GENETIC HOPES

"The great hope of the modern targeted approach was that with DNA
sequencing we would be able to find what specific genes, when mutated,
caused each cancer," said molecular biologist Mark Ptashne of Memorial
Sloan-Kettering Cancer Center in New York. The next step was to design a
drug to block the runaway proliferation the mutation caused.

But almost none of the resulting treatments cures cancer. "These new
therapies work for just a few months," Watson told Reuters in a rare
interview. "And we have nothing for major cancers such as the lung, colon
and breast that have become metastatic."

The main reason drugs that target genetic glitches are not cures is that
cancer cells have a work-around. If one biochemical pathway to growth and
proliferation is blocked by a drug such as AstraZeneca's Iressa or
Genentech's Tarceva for non-small-cell lung cancer, said cancer biologist
Robert Weinberg of MIT, the cancer cells activate a different, equally
effective pathway.

That is why Watson advocates a different approach: targeting features
that all cancer cells, especially those in metastatic cancers, have in
common.

One such commonality is oxygen radicals. Those forms of oxygen rip apart
other components of cells, such as DNA. That is why antioxidants, which
have become near-ubiquitous additives in grocery foods from snack bars to
soda, are thought to be healthful: they mop up damaging oxygen radicals.

That simple picture becomes more complicated, however, once cancer is
present. Radiation therapy and many chemotherapies kill cancer cells by
generating oxygen radicals, which trigger cell suicide. If a cancer
patient is binging on berries and other antioxidants, it can actually
keep therapies from working, Watson proposed.

"Everyone thought antioxidants were great," he said. "But I'm saying they
can prevent us from killing cancer cells."


'ANTI-ANTIOXIDANTS'

Research backs him up. A number of studies have shown that taking
antioxidants such as vitamin E do not reduce the risk of cancer but can
actually increase it, and can even shorten life. But drugs that block
antioxidants - "anti-antioxidants" - might make even existing cancer
drugs more effective.

Anything that keeps cancer cells full of oxygen radicals "is likely an
important component of any effective treatment," said cancer biologist
Robert Benezra of Sloan-Kettering.

Watson's anti-antioxidant stance includes one historical irony. The first
high-profile proponent of eating lots of antioxidants (specifically,
vitamin C) was biochemist Linus Pauling, who died in 1994 at age 93.
Watson and his lab mate, Francis Crick, famously beat Pauling to the
discovery of the double helix in 1953.

One elusive but promising target, Watson said, is a protein in cells
called Myc. It controls more than 1,000 other molecules inside cells,
including many involved in cancer. Studies suggest that turning off Myc
causes cancer cells to self-destruct in a process called apoptosis.

"The notion that targeting Myc will cure cancer has been around for a
long time," said cancer biologist Hans-Guido Wendel of Sloan-Kettering.
"Blocking production of Myc is an interesting line of investigation. I
think there's promise in that."

Targeting Myc, however, has been a backwater of drug development.
"Personalized medicine" that targets a patient's specific cancer-causing
mutation attracts the lion's share of research dollars.

"The biggest obstacle" to a true war against cancer, Watson wrote, may be
"the inherently conservative nature of today's cancer research
establishments." As long as that's so, "curing cancer will always be 10
or 20 years away."

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