Multiple Myeloma Genome Sequenced, Reveals New Therapeutic Targets

The mammothundertaking of sequencing the entire genomic multiple myeloma from tissue samples taken from 38 patients has shed light on the molecular mechanisms involved in this disease. It has also revealed some surprising potential therapeutic targets for which there are drugs already available that can be tested. The study, published in the March 24 issue of Nature , unveiled many different pathways involved in the disease, some of which were unknown previously. "A project of this scale would have been unimaginable a few years ago," said study coauthor Todd Golub, MD, from the Dana-Farber Cancer Institute, Boston, Massachusetts. He emphasized the importance of sequencing the genome from many different patients, instead of just 1 patient, to obtain a complete picture, because some mutations are not found in everypatient. The project has been "very informative," Dr. Golub noted."We can now see with greater clarity and greater precision howmolecular pathways are involved," he said, joking that the study has transformed what was previously a "transistor radio view" of the disease to a"high-definition television view." Dr. Golub was one of the speakers at a press briefing organized by the Multiple Myeloma Research Foundation (MMRF), which funded the projectto the tune of $12 million. MMRF spearheaded the project by organizing the collection of tissue samples and liaising between the various clinical sitesand basic research laboratories that were involved. Surprising Discovery One of the surprising discoverieswas that BRAF mutations are involved in multiple myeloma, but only in about 4% of patients."No one had been thinking of BRAF as a driver or a therapeutic target in multiple myeloma, but this suggests a new hypothesis, and it would be reasonable now to test BRAF inhibitors," Dr. Golub said. Such compounds are already available — in fact, a BRAF inhibitor has shown significant clinical activity in melanoma, he added. This compound, PLX0432 (developed by Plexxikon/Roche), showed, in an early clinical trial in patients with melanoma and BRAF mutation, responses in "a remarkable 81% of patients," and was hailed as a "major breakthrough" when these results were published last year ( N Engl J Med . 2010:363:809-819),as reported previously by Medscape Medical News . Via http://www.medscape.com/viewarticle/739650