Major Trends in Modern Cancer Research - Celebration, Day One

Harold Varmus welcomes guests to Major Trends in Modern Cancer Research.

Memorial Sloan-Kettering Cancer Center President Harold Varmus opened the evening by posing the question, "Why are we so excited about what's going on in cancer research today?" He explained that researchers know much more about cancer than they did 10 or 15 years ago, and, in particular, about the biochemical and genetic mechanisms by which cancers arise and behave. "This knowledge is changing dramatically and rapidly how we detect, classify, and treat cancers," Dr. Varmus said.

In talks that followed, three senior Memorial Sloan-Kettering Cancer Center investigators described research activities focusing on the intersection between laboratory investigations and the improvement of treatments for patients with cancer.

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	Joan Massagué discusses metastasis.

Joan Massagué, Chair of the Sloan-Kettering Institute's Cancer Biology and Genetics Program, discussed metastasis -- the process by which cancer cells spread throughout the body -- and how scientists are using new understandings of gene behavior to elucidate this process. "Metastasis occurs in an organ- or tissue-specific pathway," said Dr. Massagué, explaining that different sets of genes (called gene signatures) predict the likelihood that a tumor will metastasize and, in addition, dictate to which organs a particular cancer will spread. "We're now addressing what genes mediate metastasis -- in other words, allow already aggressive tumor cells to also become successful metastatic cells. And we're asking: Could such genes and the products they encode offer potential targets for therapeutic intervention through the development of pharmacological blockers of their activity?"

David Scheinberg

Taking up Dr. Massagué's theme, David A. Scheinberg, Chair of Sloan-Kettering Institute's Molecular Pharmacology and Chemistry Program, surveyed new models for cancer drug discovery and development. "Over the last several decades there's been an accelerating evolution in our concepts of how to make cancer therapies," Dr. Scheinberg said, touching on deriving drugs from natural products, high-throughput methods that can screen up to a million compounds a day for their ability to kill cancer cells, and harnessing the power of the immune system to target and eliminate cancer. Then, asking, "How do we put all this together?" he painted a picture of combining multiple therapeutic strategies, describing treatment of a hypothetical tumor that included cutting off its blood supply; delivering a small molecule to induce the process of cell death; employing an antibody to activate a pathway that selectively "goes after" the particular genetic lesion that gave rise to the tumor; and, finally, vaccinating with an antigen found on the tumor's cells to generate an immune response.

	Charles Sawyers speaks at Major Trends in Modern Cancer Research.

The problem of drug resistance in cancer was discussed by Charles L. Sawyers, Chair of HOPP, in the context of the development of Gleevec®, a drug that induces near-complete and sustained remissions in patients with chronic myeloid leukemia (CML). "Gleevec has now replaced the treatments used before for CML, including chemotherapy and bone marrow transplantation," Dr. Sawyers observed. However, he noted, the drug is not a cure. CML cells remain in the body and the disease may recur. Dr. Sawyers then examined how researchers go about studying the emergence of drug resistance and develop strategies to overcome it. "What we need to make this story complete," he said, "is to know the complete cancer genome, just as we know the sequence of the human genome. Once we have that, we'll incorporate the gene signatures that Dr. Massagué described, do genotyping tests to diagnose and classify cancers more effectively, and then 'walk over' to Dr. Scheinberg to help us make the drugs that we need to work against these mutant cancer proteins."