Oncogene obsession blinding oncologists, expert says

Medical Tribune September 2008 P6
David Brill

Cancer research has been wearing
blinders for the past 30 years, according
to a world-renowned expert who
spoke recently at the National Cancer Centre
in Singapore.
By being “obsessed with oncogenes,” the
international research community has largely
overlooked simpler targets for drug development,
said Professor Mak Tak Wah, who
believes that disrupting the metabolic pathways
of cancer cells could be the answer.
A growing volume of research shows that
cancer cells need large amounts of glucose
and fatty acids to grow and survive. Halting
this supply, Mak says, could be a way to
starve these cells and cause them to run out
of fuel.
“You could argue that targeted therapies
– 30 years of development, tens of billions of
dollars gone into anti-cancer agents – have
been a success, but I would say that on the
street, people are saying that we’ve failed.
You could argue that it’s really been a miserable
failure,” he told Medical Tribune.
“For the last 30 years, we’ve been betting
on the same horse. Is it not time for us
to think, well, what’s the payback? Some
people argue that it’s been a fantastic success
given the complexity of the problem. I argue
no, there are clearly simpler ways.”
Mak rose to scientific fame in 1984 when
his laboratory announced the first cloning
of the human T-cell receptor gene. He has
since played an important role in developing
genetically-modified mice for use in
immunological research, published over
600 research papers and won a multitude of
prestigious awards.
Current approaches to drug development
have led to some successes, Mak said, noting
that imatinib mesylate and trastuzumab can
actually save lives in some patients. Many
other drugs, however, are widely sold for
billions of dollars yet can only prolong life
by a few months.
Mak recently co-founded a company
called Agios Pharmaceuticals, which seeks
to develop drugs that regulate cancer metabolism.
He is joined in the venture by two
like-minded US professors: Craig Thompson,
who is scientific director of the Abramson
Family Cancer Research Institute at
the University of Pennsylvania, and Lewis
Cantley, chief of the division of signal transduction
at Harvard Medical School.
“We’re looking at the problem differently,”
said Mak, himself a professor at the
University of Toronto, Canada, and director
of the Campbell Family Institute for Breast
Cancer Research.
“We want to reignite this concept. You
can’t eat breakfast all day – we’ve been eating
breakfast for 30 years. Don’t you think
it’s time to change?”
The metabolism concept advocated by
the three professors has already begun to
yield results: Cantley’s group published two
papers in Nature earlier this year, identifying
the enzyme pyruvate kinase M2 as playing
an important role in the rapid growth of tumor
cells. [2008 Mar 13;452:181-6; 2008 Mar
13;452:230-3]
Others are finally beginning to take note
of these ideas, said Mak, who has been invited
to organize a session on cancer metabolism
for next year’s meeting of the American
Association for Cancer Research.
“Some people are saying ‘well let’s keep
an open mind and listen to these people.
They may be crazy but what the heck,’” he
said.
“It’s a different way. But every time you
start a wave you still need to start with a ripple.
Let’s see,” he concluded.