Two studies reported this summer by Memorial Sloan-Kettering investigators have provided new details about the genetic basis of metastasis, the process by which cancer spreads from primary tumors to sites throughout the body. Consisting of multiple processes and involving dozens of genetic mutations, metastasis poses a daunting challenge. But it is a challenge Memorial Sloan-Kettering is determined to meet, since metastasis accounts for 90 percent of all cancer deaths in patients with solid tumors.

To conduct the kind of collaborative, interdisciplinary research required to understand metastasis in all its complexity—and to promote interactions among different labs pursuing studies into its multiple aspects—Memorial Sloan-Kettering increasingly relies on the support it receives from generous benefactors along with funding from the government and other outside agencies.

One of the recent metastasis studies, reported in the journal Cell, identifies the cell-signaling pathway responsible for the rapid spread of lung adenocarcinoma to the brain and bone. Using bioinformatics to analyze large collections of lung cancer samples, researchers pinpointed two genes linked to a hyperactive WNT cell-signaling pathway—the same pathway implicated in the spread of colorectal cancer—as the reason the cancer is able to invade other organs swiftly and, once there, to spark renewed tumor growth.

According to Joan Massagué, the study’s lead author, this finding suggests that therapies targeting the WNT pathway might help prevent the rapid spread of lung cancer.

Dr. Massagué, who chairs MSKCC’s Cancer Biology and Genetics Program, was also lead author of the second study, which appeared in the July 7 issue of Cancer Cell. That research zeroes in on the very different behavior of metastatic breast cancer—namely, its ability to shed residual cells that survive initial treatment, and then take years or even decades to acquire the molecular characteristics needed to metastasize.

Using the techniques of gene expression profiling to register the activity of signaling pathways, the research team found that breast cancer cells that spread to bone marrow and survive over time contain the gene product Src. Subsequent research on mice showed that genetically disabling Src activity in human breast cancer cells kept them from surviving in bone marrow and thus prevented future metastases, pointing the way to a potential therapeutic strategy.

Taken together, the two studies highlight one of the factors that makes metastasis such a complex problem: it can follow a completely different course depending on the type of cancer involved. The ability to tackle such complex issues on multiple fronts is one of the hallmarks of the Center’s wide-ranging metastasis research enterprise, which draws on a wealth of expertise across the entire institution.

For example, the lung cancer initiative brought together scientists from the Sloan-Kettering Institute (SKI), the Center’s research arm, with colleagues from clinical departments, including Mark G. Kris, chief of the thoracic oncology service, pathologist Marc Ladanyi, chief of the molecular diagnostics service, and the late William L. Gerald, a surgical and molecular pathologist whose work spanned areas ranging from pediatric oncology to cancer genomics to prostate cancer research.

Among the investigators taking part in the breast cancer study were two prominent medical oncologists at Memorial Sloan-Kettering: Clifford A. Hudis, chief of the Breast Cancer Medicine Service, and Larry Norton, deputy physician-in-chief for breast cancer programs.

Maintaining such a collaborative environment while supporting individual projects that inform and inspire each other requires a significant investment of resources—and it is here that Memorial Sloan-Kettering’s generous supporters have provided vital impetus to ongoing progress.

Among the benefactors helping to support the Center’s intensified effort targeting metastasis is cable television pioneer Alan B. Gerry, whose 2007 commitment of $5 million established the Alan and Sandra Gerry Metastasis Research Initiative. The Gerry Initiative provided funding for both recent metastasis studies at the Center, as did the Hearst Foundations Metastasis Research Initiative, created with a $1 million gift from the William Randolph Hearst Foundations.

Additional support for the lung cancer study came from the National Institutes of Health (NIH), the Damon Runyon Cancer Research Foundation, and the American Society of Clinical Oncology. The breast cancer project received funding from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, the NIH, and the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research.

For additional information about the studies, please see:

"Research Reveals What Drives Lung Cancer’s Spread"
"Researchers Find Genetic Key to Breast Cancer’s Ability to Survive and Spread"