Memorial Sloan-Kettering Cancer Center: A Venerable Institution That Shows No Signs of Slowing Down
Founded in 1884, the New York City institute known today as Memorial Sloan-Kettering Cancer Center (MSKCC) is the world’s oldest and largest private cancer center. The facility started out as the New York Cancer Hospital. A new edifice was built in 1939, and the institution was rechristened Memorial Hospital. In the 1940s, former General Motors executives Alfred Sloan and Charles Kettering established the Sloan-Kettering Institute, which was built adjacent to Memorial Hospital, to conduct scientific medical research. The two entities consolidated in 1960, and today, MSKCC is widely recognized as one of the world’s premier biomedical research institutions and cancer care facilities. MSKCC has more than 10,000 employees, including 727 attending staff. In 2008, more than 22,000 patients were admitted to the hospital, and MSKCC’s Manhattan and regional sites cumulatively logged more than 466,000 outpatient visits.
Research has long been recognized as an essential component of patient care at MSKCC, and when it comes to cancer, the center has remained at the forefront in terms of new approaches and scientific breakthroughs. In 2006, the center opened a 23-floor research building to expand on many of its projects and take on new ones. Next door to the research building, construction is currently under way on a 7-floor laboratory. MSKCC’s enduring dedication to educating and training generations of researchers and physicians has seen the institution rewarded with a reputation among patients and the scientific community as one of the nation’s leaders on a wide range of cancers.
Linking Parkinson’s Disease and Cancer
One project MSKCC has been working on is determining possible links between Parkinson’s disease and malignancy. In 2009, Timothy Chan, MD, a radiation oncologist and member of the Human Oncology and Pathogenesis Program and the Brain Tumor Center at MSKCC, led a multidisciplinary team of the institution’s investigators to what he termed a “surprising discovery.” They found that the PARK2 gene, responsible for an inherited form of Parkinson’s disease, plays a role in several types of cancer, including colon and lung cancers and glioblastoma.
“You couldn’t really have two diseases that are more different,” explained Chan. “Parkinson’s is a neurodegenerative disease. When the neurons in the mid-brain die, the result is motor function is disrupted. In cancer, it’s just the opposite…you have uncontrolled growth, with cells spreading everywhere.”
The PARK2 gene encodes a protein known as parkin, which regulates cell division and proliferation. Chan’s team found that somatic mutations in the PARK2 gene on chromosome 6q25.2-q27 interfere with parkin’s ability to ubiquitinate and degrade cyclin E. Accumulation of cyclin E accelerates the cell cycle and cell division becomes rampant, increasing the likelihood of cancer. Chan suspects a similar process is at work in Parkinson’s, which is associated with germline mutations in this same area of the chromosome. The cyclin E builds up in the neurons, inciting them to attempt to divide. The problem is that the neurons cannot divide and consequently die. The area on chromosome 6 where these PARK2 mutations are found is known to play a contributing role in many types of cancer.
Chan said his team’s discovery provides a conceptual framework for combating and treating different forms of cancer. “This defines a pathway in which cancers grow more and more aggressively and out of control,” he explained. “It helps explain all the tumors with chromosome 6 loss, which is a large number. From a pure numbers perspective, this finding identifies the gene and hence the pathway responsible.” Chan said now that they have determined the pathway involved, researchers can examine it for targets that might prove useful in inhibiting the undesirable oncogenic behavior.
Chan believes the MSKCC group’s discovery will open doors not only in cancer research, but also in Parkinson’s. “I think the neurologists and people studying Parkinson’s disease as a neurologic disorder will have a clue now to look for events that cause the disease in the general population.”
Moving forward, Chan said new research will focus on developing animal models to test therapeutics in development that might target the disruptive pathway. “We’re now able to make some sense in an intellectual framework that explains the primary defect in a lot of different cancers,” he added.
Using Molecular Diagnostics
Researchers at MSKCC believe that the key to treating men and women with lung cancer lies in gaining a better understanding of the genetic makeup of each person’s tumor. By using molecular diagnostic testing to pinpoint specific mutations associated with more than one-third of lung cancer cases, oncologists maximize the chances of treatment success.
Marc Ladanyi, MD, is chief of MSKCC’s Molecular Diagnostics Service and director of the Diagnostic Molecular Pathology Laboratory. He has been much more than an eyewitness to the growth of molecular diagnostics over the last two decades.