NEW YORK (GenomeWeb) – Memorial Sloan Kettering Cancer Center today announced the creation of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology (CMO) to "reshape clinical trials" and accelerate the translation of new molecular discoveries into medical care.
The CMO was launched with a $100 million gift from the Marie-Josée and Henry R. Kravis Foundation.
"Memorial Sloan Kettering has already proven itself to be a leader in understanding cancer at the genetic level and in putting that knowledge to work for patients," Henry Kravis said in a statement. "The new Center for Molecular Oncology will take these efforts to an entirely new level."
The center will bring together researchers and facilities already in the MSKCC network as well as create new facilities and recruit new faculty. It will house two in-house next-generation sequencing facilities, one to sequence patients in real time, the other to be used for the discovery of new genetic alterations and drug targets. Additionally, new lab space is being constructed and the CMO is purchasing new state-of-the-art instruments for generating and analyzing large-scale genomic data, MSKCC said.
Among the work that will be carried out at the CMO is the profiling of archived tumor samples and tissues from clinical trials by next-generation sequencing and other molecular methods. The molecular information from each tumor will be correlated with clinical outcomes to provide insights into the importance of genetic alterations in tumors and how that information can be used for more effective treatments.
MSKCC said the new center aims to analyze more than 10,000 patient tumors in its first year "with an eye toward offering molecular analysis for every type of cancer and for all [MSKCC] patients." It also plans to enroll patients in phase I clinical trials called basket studies, in which patients with tumors that test positive for certain mutations will be offered therapies regardless of cancer types.
"The location of a tumor, such as breast or lung cancer, is becoming less important than the genomic information of the tumor, and basket studies include many more people than a disease-specific trial," José Baselga, physician in chief of Memorial Hospital, said. "A therapy designed for a specific mutation could benefit everyone whose tumor has that mutation."
MSKCC's Genomics Core Laboratory will help process, automate, and sequence tumor samples, and bioinformatics researchers will analyze the data. MSKCC's Center for Mechanism-Based Therapies will work with the CMO to bring new findings to the clinic by translating newly discovered mutations into therapies that can be tested in clinical trials.
In total, the CMO will include about 20 labs and support more than 100 faculty and staff at MSKCC, it said.
The CMO will retrospectively analyze tumors of exceptional responders, or patients who have a sustained response to treatment in a clinical trial even though almost all the other patients in the trial don't. MSKCC noted that research by David Solit, the inaugural director of the CMO, identified the biological basis for an exceptional responder to everolimus, which goes by the brand name Afinitor, a targeted therapy approved for treating kidney cancer.
Through whole-genome sequencing on the exceptional responder, Solit discovered a mutation in the TSC1 gene, which is known to activate the mTOR pathway. Everolimus targets the pathway. MSKCC researchers then developed a basket study involving patients whose tumors test positive for TSC1 mutations. Patients in the study will be offered the drug.
MSKCC also noted that CMO Associate Director Michael Berger developed a new test for screening mutations in 341 cancer-associated genes. MSKCC will use the test — called the Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) test — to help screen more than 10,000 patients annually for genetic mutations that may predict sensitivity to new cancer therapies, it said.
The CMO will also use the IMPACT test for the sequencing of healthy cells and tumor cells in all patients with metastatic disease in order to discover why tumors spread and why patients may be predisposed to cancer, Solit said.
"It's likely that these discoveries will also lead to improved treatments for patients with earlier stage disease because the same genetic markers may aid in the identification of patients who need more aggressive therapy upfront, or who can be spared certain treatments that offer no benefit," he said.
The CMO will support new assay development, including those that expand the number of genes for analysis beyond the 341 covered by the IMPACT test, and it will develop new methods of liquid biopsies that genetically profile tumors by identifying DNA mutations released by a tumor into the blood. New assays also "are being explored" for the detection of mutations and the monitoring of therapies at the molecular level to determine whether they work.
"The vision for the CMO is nothing less than to revolutionize the treatment of cancer," Solit said. "Our integrated clinical and scientific teams coupled with our ever-increasing genetic sequencing capabilities will allow us to build upon the molecular insights we've gleaned over the past decade to accelerate the development of more effective and less toxic cancer therapies."