Cancer Cell reports critical step to speed molecularly targeted therapeutics for multiple myeloma
NORWALK, Conn.--(BUSINESS WIRE)-- The Multiple Myeloma Research Foundation (MMRF) today hailed a new publication in Cancer Cell as a major step forward in the organization's efforts to advance precision medicine in the treatment of myeloma through the most comprehensive characterization of the myeloma genome to date. Researchers from the Broad Institute, the Translational Genomics Research Institute, the Multiple Myeloma Research Consortium (MMRC) and the MMRF today published an analysis of 203 multiple myeloma genome sequences, expanding upon the original set of 38 published in Nature in 2011.
The data identified significantly mutated genes, genetic alterations and pathways that may respond to molecularly-directed therapies or drug combinations and pave the way to precision medicine. In this analysis, specifically, researchers were able to identify new genetic lesions that had not been observed in the original set of 38 sequences, which, at the time, had been the largest set of whole genome sequences published in any cancer. Most excitingly for patients, some of the new molecular alterations identified may be amenable to near-term precision trials because there are FDA-approved treatments for other types of cancer that could be repurposed for myeloma. Additionally, the findings provided further evidence that genetically distinct clones of myeloma exist within an individual patient, an observation that will have important clinical implications.
"Today's publication would not have been possible without extraordinary partners working side by side with us over the last eight years to enable the tissue collection and processing as well as molecular profiling and data analysis," said Walter Capone, President of the MMRF. "We look forward to continuing our collaboration with these and other world-class centers to conduct clinical trials in molecularly-defined subtypes of patients, which will accelerate precision medicine and a cure for multiple myeloma. A network of many motivated centers working together is critical to accomplish such an effort in an uncommon and heterogeneous cancer like multiple myeloma."
Previous genomic studies using a small number of samples hinted at clonal diversity in myeloma. This present effort, because of its size and the high-resolution analytical approaches used, is unprecedented in its comprehensiveness to precisely assess the clonality within a patient's disease and the distribution of identified mutations. For example, one third of multiple myeloma patients with a BRAF V600E mutation also harbor a clone with a KRAS or an NRAS mutation. The work presented suggests that just like in other cancers, BRAF inhibitors in the clinic might actually promote the growth of those KRAS or NRAS mutated multiple myeloma clones, reinforcing the need for accurately identifying the molecularly-based therapeutic approaches in such cases.
The work was conducted as part of the $12 million Multiple Myeloma Genomics Initiative (MMGI), a progressive genome-mapping program spearheaded by the MMRF beginning in 2005 to significantly advance the biological understanding of the disease leading to more precision-based therapeutic approaches. The analysis was conducted using a combination of whole-genome sequencing and whole-exome sequencing, performed on patient samples collected via the MMRC, a network of 16 collaborating academic medical centers, and processed by centralized tissue bank housed at the Mayo Scottsdale. All of the data generated through this project will be made publicly available to cancer researchers worldwide through the Multiple Myeloma Genomics Portal. Funding for the project and the portal has been provided by the MMRF.
"The MMRF has played a key, collaborative role in this work. The Foundation's support and the samples provided by the MMRC enabled the discoveries highlighted in our paper, and set the stage to advance our understanding and treatment of multiple myeloma," said co-senior author Todd Golub, the Broad Institute's Chief Scientific Officer and Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute. Golub is also a professor at Harvard Medical School and an investigator at Howard Hughes Medical Institute. "This important work would not have happened without their vision and commitment to advancing this program over the last eight years."
To continue the momentum of these study findings, the MMRF has initiated a series of Precision Medicine initiatives including CoMMpass (Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile), a landmark longitudinal study of 1,000 newly diagnosed patients with comprehensive molecular profiling and clinical data collection over the course of the patient's disease. In 2014, the MMRF is also planning to initiate a number of clinical trials with targeted agents in molecularly-selected patients.
About the Multiple Myeloma Genomics Initiative (MMGI)
The MMGI is a $12 million program that comprises several research and discovery efforts spanning the spectrum of genome science. The MMRC contributes patient samples from its 16 collaborating academic members via a centralized Tissue Bank; the MMRF provides funding for the project. The comprehensive genomic survey of MMRC samples is conducted in collaboration with the Broad Institute and the Translational Genomics Research Institute (TGen). The MMGI comprises several research and discovery efforts spanning the spectrum of genome science. Array comparative genomic hybridization (aCGH), gene expression profiling (GEP), DNA methylation analysis and DNA sequencing are among the assays performed on hundreds of patient multiple myeloma tumor tissue. Data from the MMGI and other multiple myeloma genomics efforts is available to the scientific community through the Multiple Myeloma Genomics Portal, (www.myelomagenomics.org).
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer. The five-year relative survival rate for multiple myeloma is approximately 43 percent, one of the lowest of all cancers. In 2013, more than 22,000 adults in the United States will be diagnosed with multiple myeloma and nearly 11,000 people are predicted to die from the disease.
About the Multiple Myeloma Research Foundation (MMRF)
The Multiple Myeloma Research Foundation (MMRF) was established in 1998 as a 501(c)(3) non-profit organization by twin sisters Karen Andrews and Kathy Giusti, soon after Kathy's diagnosis with multiple myeloma. The mission of the MMRF is to relentlessly pursue innovative means that accelerate the development of next-generation multiple myeloma treatments to extend the lives of patients and lead to a cure. As the world's number-one private funder of multiple myeloma research, the MMRF has raised over $240 million since its inception and directs 90% of total budget to research and related programming. As a result, the MMRF has been awarded Charity Navigator's coveted four-star rating for 11 consecutive years, the highest designation for outstanding fiscal responsibility and exceptional efficiency. For more information about the MMRF, please visit: www.themmrf.org.
About the Multiple Myeloma Research Consortium
The Multiple Myeloma Research Consortium (MMRC) is a 509(a)(3) non-profit organization which integrates leading academic institutions to accelerate drug development in multiple myeloma. It is led from MMRC offices in Norwalk, Conn., and comprises 16 member institutions: University of California, San Francisco, City of Hope, Dana-Farber Cancer Institute, Emory University's Winship Cancer Institute, the Cancer Center at Hackensack University Medical Center, H. Lee Moffitt Cancer Center & Research Institute, Mayo Clinic, Ohio State University, Mount Sinai School of Medicine, University Health Network (Princess Margaret Hospital), University of Chicago, University of Michigan, Washington University, Baylor Charles A. Sammons Cancer Center, Sarah Cannon Research Institute and Virginia Cancer Specialists. The MMRC was founded in 2004 by Kathy Giusti, a myeloma patient, and with the help of the scientific community. The MMRC is a sister organization to the Multiple Myeloma Research Foundation (MMRF), the world's leading funder of multiple myeloma research. The MMRC is widely recognized as an optimal research model to rapidly address critical challenges in drug development and to explore opportunities in the today's most promising research areas in genomics, compound validation, and clinical trials. The MMRC is the only consortium to join academic institutions through membership agreements, customized IT systems, and an integrated tissue bank. For more information, please visit www.themmrc.org.
MMRF Anne Quinn Young 203-652-0212 (office) 203-536-8691 (mobile) email@example.com
Source: Multiple Myeloma Research Foundation
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