When it comes to tackling cancer, James D. Watson thinks it's biochemists' turn to shine. In an op-ed for yesterday's New York Times, Watson, who received a Nobel Prize for unraveling the structure of DNA, describes what he thinks is the way to new therapies that get at the root cause of cancer. The answer lies not in the genetic mutations involved in various cancers, but in tumor cells' chemical machinery and metabolism, he writes. Watson also pushes for more emphasis on combination therapies for cancer, and a better balance in funding for basic and clinical cancer research. The Curious Wavefunction posted a great take on the editorial this morning, and I thought I'd expand on some of the thoughts posted there.
In particular, Watson calls attention to the work of biochemist (and fellow Nobelist) Otto Warburg, who in the 1920's observed that cancer cells metabolize glucose differently from cells in healthy tissues. He mentions that studies from the past year had further illuminated the meaning of Warburg's discovery, and then advocates a particular target:
This discovery indicates that we need bold new efforts to see if drugs that specifically inhibit the key enzymes involved in this glucose breakdown have anti-cancer activity.
Watson seems to be referring to a pair of 2008 studies from Nature, as well as a review article that appeared in Science last May.
Science2009, 324, 1029.
Nature2008, 452, 181.
Nature2008, 452, 230.
The studies, from a team led by Lewis C. Cantley at Harvard Medical School, explain that tumor cells express a particular form of pyruvate kinase, the enzyme that catalyzes the final step in the glucose breakdown process known as glycolysis. This same form of pyruvate kinase shows up in other rapidly developing cells such as those in a fetus or embryo, but not in slower-growing adult cells. Work in the two studies suggests that it may be possible to target that specific form of pyruvate kinase to take on cancer. The idea of targeting specific forms of an enzyme might be a general strategy for taking on cancer, because many enzymes besides pyruvate kinase have multiple forms, Cantley adds. Cantley has since co-founded a company called Agios Pharmaceuticals inspired by this technology, and he sits on Agios's board of directors. Watson is not affiliated with Agios, Cantley tells C&EN.
The human genome sequence gave researchers "a candy store of information to pursue," Cantley says. But once researchers know that a given mutation is associated with cancer, it's not always easy to figure out why that mutation leads to a given biological state. "That's where the realm of biochemistry comes in," he adds.
It's still too early to tell how Agios's strategy will play out, but it's a good idea to look beyond genetics and take a more integrative view of what's happening in a cancer cell. Cancer is a tremendously complex disease - why should the solution to the problem lie only in our genes? We've got more and better tools than ever before to probe the basic biology and chemistry of cancer, so there's no better time to push some more money toward basic, or what Watson calls pure, cancer research.
For more commentary on the op-ed, check out PSA Rising (contains video!).