Monoclonal Antibodies-Lecture

Ronald Levy is an American medical doctor and scientist at Stanford University. He specializes in lymphoma, including Non-Hodgkin's Lymphoma, Burkitt's Lymphoma and Hodgkin's Disease His research investigates how the immune system can be harnessed to fight lymphoma. His work has led to the concept that antibodies can be used as personalized anticancer drugs and to the development of an antibody-based drug, Rituxan, that is widely used to treat lymphoma

How Cancer Begins

If you’re worried about getting cancer, do yourself a favor: steer clear of red meat and rich foods, and avoid cigarettes. In this lecture, Robert Weinberg provides the scientific basis for this commonplace advice, as well as a layman’s look at the genetic, biochemical and environmental factors that make good cells go bad.

Normal cells are civic-minded, lining up together in a precise architecture that gives structure to body tissue. When the cell’s genes are damaged, they send out faulty instructions, turning orderly structure into a chaotic mess. This kind of injury to cells likely comes from the outside – as many as 90% of human cancers are due to bad diets and smoking. Weinberg wants to understand the specific pathways by which the cells’ enemies invade and do their damage, in hopes of then being able to halt the process and freeze a cancer’s growth. But, cautions Weinberg, better to count on prevention than a cure in the fight against cancer.

About the Speaker

Robert A. Weinberg '64, PhD '69

Founding Member, MIT Center for Cancer Research

Member, Whitehead Institute Daniel K. Ludwig and American Cancer Society Professor for Cancer Research
Department of Biology

Robert A. Weinberg has earned some of the top honors in his field. Most recently, he won the 2006 Landon-AACR Prize for Basic and Translational Cancer Research. He is also a 1997 National Medal of Science awardee.

Weinberg's laboratory discovered the first human oncogene and the first tumor suppressor gene. Today, much of his research focuses on new models of breast cancer development including the stages of tumor invasiveness and metastasis.

He earned his Ph.D. in biology from MIT in 1969, and was one of the Founding Members of the MIT Center for Cancer Research in 1973. He was appointed a professor at MIT in 1982, the same year he joined the Whitehead Institute. Weinberg was named American Cancer Society Research Professor in 1985 and received the Daniel K. Ludwig Professorship for Cancer Research in 1997. He is a member of the National Academy of Sciences and the Institute of Medicine.

Cancer Lecture by Robert A. Weinberg

About Speaker
Robert A. Weinberg '64, PhD '69
Founding Member, MIT Center for Cancer Research

Member, Whitehead Institute Daniel K. Ludwig and American Cancer Society Professor for Cancer Research Department of Biology

Robert A. Weinberg has earned some of the top honors in his field. Most recently, he won the 2006 Landon-AACR Prize for Basic and Translational Cancer Research. He is also a 1997 National Medal of Science awardee.

Weinberg's laboratory discovered the first human oncogene and the first tumor suppressor gene. Today, much of his research focuses on new models of breast cancer development including the stages of tumor invasiveness and metastasis.

He earned his Ph.D. in biology from MIT in 1969, and was one of the Founding Members of the MIT Center for Cancer Research in 1973. He was appointed a professor at MIT in 1982, the same year he joined the Whitehead Institute. Weinberg was named American Cancer Society Research Professor in 1985 and received the Daniel K. Ludwig Professorship for Cancer Research in 1997. He is a member of the National Academy of Sciences and the Institute of Medicine.

Metastasis Lecture

No diagnosis of cancer is welcome, but some scenarios are more dreaded than others. Richard Hynes discusses what happens “when cells in the primary tumor lose their sense of address and wander off to places they’re not supposed to go.” His talk lays out the process of invasion, by which the cancer spreads into tissues adjacent to the tumor, and that of metastasis, where the cancer disseminates to distant sites.

Hynes describes the transitions a cancer undergoes as it spreads. He explains how tissue in our bodies is made of sheets of epithelial cells that are carefully arranged on a “basement membrane” by a series of adhesion receptors. These receptors, if functioning properly, don’t usually allow the cells to go anywhere. When a cell becomes tumorigenic, it loses some adhesion, and then if it becomes more damaged “wanders off into the underlying tissue.” This is called invasion. Hynes and other researchers are looking at the molecules responsible for cells’ adhesive qualities, and at the mutations in genes that trigger a loss of adhesion. Some of these processes are part of normal development, but occasionally, a “switch gets thrown in cells that should have stayed epithelial” and they become migratory instead.

 

Once on the move, cancer cells “need plumbing to grow,” says Hynes. Tumors recruit blood vessels to feed them and remove waste, and they can also exploit the body’s white blood cells and platelets to promote their own growth. Hynes describes “cross talk between tumor cells and cells in bone,” where the “two cells get together in evil combination to damage the bone and enhance the growth of metastases.” Scientists have discovered “a lot of different mechanisms by which metastatic cells learn new tricks and suborn the mechanism of the host to get them where they’re going.” Hynes finds such insidious workings an “appealing thing, since these alterations offer opportunities for therapies.” Researchers can tinker with circuits between cells, restore growth suppression and interfere with blood vessel recruitment. It’s “a complex problem,” says Hynes, but there are “lots of ways to get at this.”

About the Speaker

Richard O. Hynes PhD

Daniel K. Ludwig Professor for Cancer Research, Department of Biology Investigator, Howard Hughes Medical Institute

Richard Hynes received his B.A. in biochemistry from the University of Cambridge, U.K., and his Ph.D. in biology from MIT. After postdoctoral work at the Imperial Cancer Research Fund in London, where he initiated his work on cell adhesion, he returned to MIT as a faculty member.

Hynes is a fellow of the Royal Society of London, the American Academy of Arts and Sciences, and the American Association for the Advancement of Science, and a member of the National Academy of Sciences and the Institute of Medicine. He has received the Gairdner Foundation International Award for achievement in medical science and recently served as president of the American Society for Cell Biology.

New Lessons in Cancer Research

Cancer is a conniving enemy. Try to kill it off through surgery or chemotherapy, and it finds a way to sneak back in. Jacqueline Lees tells an engaged Soap Box audience what insights and tools research now offers in the longstanding battle against this relentless disease.

Big gains have come from molecular study of tumors at different stages, Lees says. It often takes many years for a cancerous cell to develop into a dangerous tumor, one that can yield metastases. There might be six phases of development over 15 years in a cancer’s evolution, and scientists have formed a good understanding of what these different lesions look like in various cancers, and how they behave. Lees calls this process “actually a beautiful example of evolution,” since the cell that mutates and begins to divide uncontrollably evolves to become more successful relative to other cells in the tissue.

 

Other research focuses on the genetic basis of cancers. Two “flavors” of genes appear responsible for provoking cancerous changes in cells: oncogenes and tumor suppressor genes. It may be possible to intervene along the genetic pathways underlying cancer growth, says Lees. Her own work, involving mutant mice and zebrafish, hopes to identify the mechanisms involved in specific kinds of tumors, and to figure out ways of inhibiting cancer cell growth. Understanding the nature of specific cancers might help prevent treating people with chemical agents that don’t work for their kind of cancer, and that actually increase their tumor’s growth.

With the advent of fast and inexpensive genetic screens, it may soon be possible to determine whether each of us carries genes that predispose us toward certain kinds of cancers. But Lees questions the universal adoption of DNA testing, not just because of privacy concerns, but because there may very well be no known cure if a predisposition to disease is found. “If we sequenced every baby, and said you’re highly predisposed to a cancer, and there’s nothing we can do, would that be information people want to have?” Lees wonders. “If we could find a rapid way to sequence small subsets of genome, identify people with high risk and we could treat them if we knew they had those diseases, there’d be an argument for that, much as we do testing for diseases where we know can intervene if find children carrying them,” says Lees.

About the Speaker

Jacqueline Lees SM '86, PhD '90

Associate Director
MIT Center for Cancer Research;
Professor of Biology

Jacqueline Lees' research is focused on identifying the proteins and pathways that play a key role in tumorigenicity and establishing the mechanism of their action in both normal and tumor cells. Her lab uses a combination of molecular and cellular analyses, mutant mouse models and genetic screens in zebrafish.

Lees received her Ph.D. in 1990 from the University of London.

Computational and Systems Approaches to Cancer

Early on in his lecture, Michael Yaffe serves up an amazing fact: If the distance between each DNA base pair were one foot apart, then each time a cell divided, it would have to copy 568 thousand miles of DNA. This, says Yaffe, is enough to go around the circumference of the earth more than 22 times. What’s more, the cell has to copy its DNA with no errors. “I don’t know (if) civil engineers ... could make 10 miles of road without making single error,” says Yaffe.

Yaffe’s in the business of exploring and mathematically mapping the elaborate signal pathways inside cells that sense broken DNA and coordinate damage response. While studying one such process, cell death in the colon, Yaffe found that the traditional biochemistry approach -- picking one molecule, one stimulus and one readout-- doesn’t work. “It’s like the blind man feeling the elephant’s tail, and saying it’s a long, thin animal.” Yaffe learned that one signal may activate a series of proteins, triggering an amplification loop. A slight change might yield a “whopping response.”

In the 12 hours a cell takes to copy its DNA to create two daughter cells, “it goes to great pains to make sure everything is done correctly. It initiates checkpoints, like border crossings.” Because everyday life exposes DNA to all kinds of damage, cells have evolved “an elaborate surveillance mechanism” to “blow the whistle, signal repair, and recruit repair machinery,” or if damage is too great, essentially commit suicide. If something goes wrong with this mechanism at crucial times during cell division, cancer frequently results.

 

Just as engineers test integrated circuits at a variety of points, Yaffe came up with a method of testing cell signaling with a variety of proteins. His team came up with 7,000 signaling measurements in 760 dimensions, and 1,400 signal responses. But this data-heavy model for predicting which molecules lead to cell death didn’t satisfy Yaffe. With additional mathematical sleight of hand, Yaffe’s group boiled down the cell signaling measurements to what Yaffe calls two “canonical super axes”: “a global measure of cell stress and death, and another of survival signaling.” He hopes to use this slimmed-down model to think about drugs targeting cancer and inflammation.

About the Speaker

Michael Yaffe

Howard S. and Linda B. Stern Associate Professor of Biology, Department of Biology and the Center for Cancer Research

Michael Yaffe received his Ph.D. in Biophysical Chemistry in 1987, and an M.D. in 1989, both from Case Western Reserve University. Before MIT, he served as a surgeon in teaching hospitals in Cleveland and the Boston area, including the Harvard Medical School.

He received multiple teaching awards from University Hospitals of Cleveland, and earned the 1998 Howard Hughes Physician Scientist Award, and the 1999 Burroughs Wellcome Career Development Award.