The Scientist Blog: How to starve a tumor

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http://www.the-scientist.com/blog/display/55502/

How to starve a tumor

Posted by Tia Ghose

[Entry posted at 11th March 2009 07:00 PM GMT]

Calorie-restricted diets are thought to protect against cancer and slow tumor

growth, and a new study published in this week's Nature begins to tease out why

the measure works for some tumors, and not for others.

For almost a century, researchers have known that fasting helps animals live

longer and avoid some cancer, " but which type of cancers would be amenable to

this approach, from a therapeutic standpoint, is still an open question, " said

Pier Paolo Pandolfi, a cancer geneticist at Harvard Medical School and Beth

Israel Deaconess Cancer Center in Boston, Mass., who was not involved in the

study. The study is exciting because it is one of the first to start answering

that question at the genetic level, he said.

A team led by Sabatini, a Medical Investigator and

molecular biologist at the Whitehead Institute and the Massachusetts

Institute of Technology, injected mice with cells from six human cancer cell

lines, including breast, colon, brain, and prostate cancers. The team then

subjected half the mice to a draconian 40% cut in calories, while the rest ate

as much as they liked.

" Contrary to what we expected, not all the tumors responded, " Sabatini

said. Cutting calories slowed growth in only three of the six cell

types--breast and colon cancer cells. For the diet-responsive cell lines, tumors

in the fasting mice were between two-thirds and a fifth the volume of those in

their freely-eating counterparts.

To tease out the difference between the diet-responsive and

diet-insensitive cancers, they cultured each cell type with different

amounts of insulin and insulin growth factor 1 (IGF1) in the growth

medium. The cells that responded to calorie reductions flourished with

increasing levels of insulin and IGF1, while the diet-insensitive cells " didn't

really seem to care much about insulin and IGF1, " Sabatini said.

The group suspected that the mechanism at play involved a signaling

pathway responsible for regulating cell growth, phosphoinositide 3-kinase/Akt

(PI3k/Akt). By scanning the genetic sequence of specific proteins in the

PI3K/Akt pathway, they identified mutations in the diet-insensitive cell lines

that kept the pathway switched on. That helped the diet-insensitive tumors keep

growing, regardless of the amount of insulin they had access to.

" This paper ought to stimulate people to look at this in human cancers, " said

Lew Cantley, a systems biologist at Harvard Medical School and Beth Israel

Deaconess Hospital in Boston, Mass., who was not involved in the study. It would

be too costly and slow to evaluate the question in the general population, since

large numbers of people would have to be followed for about a decade to get

results. Furthermore, patients who have already been diagnosed with cancer

generally undergo chemotherapy or radiation almost immediately. Asking patients

who are already suffering from nausea, weight loss, and other side effects of

their treatment to comply with such a stringent diet is not feasible, he said.

Instead, one possibility would be to study dietary restriction in people with an

elevated risk of cancer, since they wouldn't have to be monitored for as long.

People with early-stage prostate cancer, for example, often don't undergo

treatment right away, but instead are closely monitored to see if the tumor

grows. Women who have had breast cancer would also be good candidates, because

they have a higher risk of forming metastases.

Even so, Cantley noted, it won't be easy. " The problem is people always cheat on

their diet, " he said.

[Guest guest]

[snip]

> " Contrary to what we expected, not all the tumors responded, "

> Sabatini said. Cutting calories slowed growth in only three

> of the six cell types--breast and colon cancer cells. For the

[snip]

> (IGF1) in the growth medium. The cells that responded to

> calorie reductions flourished with increasing levels of

> insulin and IGF1, while the diet-insensitive cells " didn't

> really seem to care much about insulin and IGF1, " Sabatini said.

Wow, what an intriguiging study, and it certainly puts more weight in the " down

with IGF1! " camp of CR, at least if you're high risk for breast and colon

cancer....