Gaining Ground

Are decades of explorations into the most dreaded of chronic diseases finally beginning to pay off in a major way?

At a time when a national newsweekly’s cover features a tumor-fighting molecule under the heading “Cancer Killer,” that may look like an excellent bet. But Tyler Jacks, assistant professor of biology in MIT’s Center for Cancer Research, says a degree of caution may be in order.

Scientists are indeed unlocking critical secrets about cancer. In fact, there’s evidence a natural agent called p53–the newsweekly’s “cover” molecule, and possibly the most famous entity with nothing but initials and numerals in its name since “Star Wars” robot R2D2–is itself a key to many malignancies.

P53, a normal component of all our cells, is a tumor suppressor. And the gene that triggers its manufacture seems to be mutated–chemically altered–in many cancers. “Roughly 60 percent of tumors carry a mutation in this gene,” notes Jacks. “That includes many of the major cancers: lung, colon, skin, breast.”

Why not just put a normal version of the gene into such tumors? That approach is actually being tested. But Jacks says neither this nor any of the other new approaches under study is likely to offer comprehensive answers. “Cells in a tumor are highly variable,” he notes, “and there’s always the risk that some will escape the effects of any type of therapy.”

Still, that doesn’t mean markedly improved treatments are out of reach. In fact, Jacks himself is in the thick of efforts to explore the workings of p53 and similar agents in hopes of fostering better approaches to cancer.

Apprenticing with a Pioneer

The faculty member, son of a former professor at the MIT Sloan School, didn’t originally plan a career exploring cancer. Yes, he liked high school biology. But he liked a lot of other things, too, from playing sports to rebuilding decrepit cars. (”I had a good time in school,” he says.)

When he began studying cancer biology at Harvard, Jacks got hooked. Still he wasn’t sure how to pursue this interest: should he become a physician-scientist? Or, should he focus solely on research?

Jacks kept the issue open into his graduate career at the University of California at San Francisco, but ultimately the lure of research proved too strong. “It’s not easy to describe what it’s like to discover something that no one in the world has ever known,” he says, “but it’s a great feeling.”

In 1988, Jacks returned East to work with Robert Weinberg. Weinberg, a member of the Whitehead Institute for Biomedical Research as well as an MIT biology professor, was the first to pinpoint a mutant gene that promotes human cancer. He later made what may turn out in retrospect to have been a still more momentous discovery, becoming the first to identify a gene that suppresses the disease.

“Bob is very creative with respect to cancer,” says Jacks. “He generates lots of useful ideas, and he was highly supportive of my work.”

A Destroyer of Cells

Exposure to mentors like Weinberg has helped Jacks make significant discoveries of his own. His group was the first to show that p53 can act as a kind of cellular suicide pill. “We demonstrated that many types of cells require p53 to destroy themselves,” he notes. And he and two MIT colleagues made the critical discovery that some cancer drugs work by harnessing this natural agent’s destructive powers.

“Tumors with functional p53 are much more sensitive to chemotherapy than those without it,” Jacks notes.

Such discoveries can help point the way to future strategies–for example, creating therapies that work even when normal p53 isn’t there to aid them. Such treatments could lie years off, Jacks concedes, but he adds that the often-lengthy time required to translate lab findings into treatments shouldn’t obscure an outlook that may be brighter than it has ever been.

For one thing, much current research is focused on phenomena that affect many types of tumors, with p53 being a prime example.

Then, too, the research tools available today have sharply boosted the rate of progress in exploring cancer. “What would have taken 10 years when I first got interested in cancer biology might take a year now,” notes Jacks, “and we can do things we simply couldn’t do before.”

Finally, there’s the accumulating knowledge about what goes wrong in cancer. “We’ve seen big improvements in our understanding of many of the genetic events involved in cancer over the past four or five years,” says Jacks. “That will only increase in the years ahead. Then, the challenge is to translate that knowledge into new treatments.”

by Richard Anthony

On Topic: cancer research, faculty, genetics