Research Focuses on Cancer Metabolism

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Research Focuses on Cancer Metabolism

Lewis Cantley, PhD, is targeting cancer's Achilles heel.

BOSTON -- May 1, 2009

The seemingly impervious cancer cell has a dramatic weakness: A kink in its metabolic functioning means that it needs more nutrients than normal cells do to survive.

Lewis Cantley, PhD, aims to exploit this fatal flaw.

“By blocking nutrients, you can effectively starve cancer cells of the fuel they need to grow and function,” explains Cantley, the Director of the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC). “This shortcoming is, in effect, the Achilles heel of cancer.”

This unique feature is also the basis for the emerging field of cancer metabolism. Bridging two established areas of research – oncology and metabolism – cancer metabolism focuses on the unique ways that cancer cells use energy, and is one of the most exciting avenues to emerge in cancer research in recent years.
Cantley is cofounder of Agios Pharmaceuticals, the first biotechnology company to focus on cancer metabolism in its pursuit of new cancer therapies. BIDMC entered into a technology license agreement with the Cambridge-based company in January 2009.

“It’s really exciting for us to play a role in moving this cutting-edge technology closer to clinical applications and patient care,” notes Christine Jost, PhD, Associate Director of BIDMC’s Technology Ventures Office (TVO). “It’s a testimony to the excellence of the research that the company has been funded in the midst of such a tough economic climate.”

Agios was founded by Cantley, together with Tak Mak, PhD, of the University of Toronto and Craig Thompson, MD, of the University of Pennsylvania, as part of a $33 million Series A financing made by Flagship Ventures, Third Rock Ventures and ARCH Venture Partners. The deal represents one of the largest venture-capital funded deals of the past year.

“Much of the early planning for the formation of the company was conducted in BIDMC’s TVO offices in 2008,” explains Jost. Now located in Cambridge, the company plans to advance its research both in the United States and in laboratories in China.

Exploiting Cancer’s Achilles Heel

Cantley’s investigations identifying oncogenes and tumor suppressors helped pave the way for this new area of investigation. “Decades of research have demonstrated that cancer cells mutate to develop hundreds and even thousands of highly complex mechanisms to ensure their survival and growth,” notes Cantley, the William Bosworth Castle Professor in the Department of Systems Biology at Harvard Medical School. “It’s now becoming clear that the primary function of many oncogenes and tumor suppressor genes is actually to modulate the metabolic functioning of cancer cells.”

With last year’s publication of an article in the journal Nature describing how tumor cells require an embryonic form of pyruvate kinase (PKM2) to control glucose metabolism, Cantley’s laboratory found itself closing in on cancer’s Achilles heel.

“Most normal tissues in adults make use of the PKM1 version of this protein for their energy purposes,” explains Cantley. “When cancer cell lines have their PKM2 protein replaced with PKM1, their ability to form tumors is impaired.”

The study, which demonstrated how cancer cells “switch on” the same highly active metabolizing enzymes as those found in fetal cells – in order to promote extremely rapid growth – explains why cancer cells are able to divide and grow better than normal cells.

“The intersection of two major areas of research – oncology and metabolism – represents an important and novel approach to targeting this deadly disease,” he adds. “And although the initial focus of Agios Pharmaceuticals will be to develop drug candidates that disrupt the growth and survival of cancer, going forward, these same rules may very well apply to other areas, including autoimmune, inflammatory and neurological diseases.”

Learn more about Cantley's work.

Read the press release describing Cantley’s PKM2 discovery.

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