Effort to improve treatment of people with rare disease still a work in progress Share Comment "We are working for the day when patients are treated on a just-in-time, individualized basis." With the recent FDA approval of the first targeted therapy for patients with a type of rare bone marrow cancer, it may seem like the United States is at the cutting edge of translational research. But despite the advances in identifying biomarkers, or indicators of disease activity, that have been made to help doctors assess how aggressive or aggressive to treat people with an extremely rare disease, scientists still lack an understanding of what underlies the disease. Scientists at the Broad Institute and Dana-Farber Cancer Institute at Harvard Medical School (HMS) have embarked on a program to identify molecular subtypes of a rare bone-marrow cancer called chronic myelomonocytic leukemia (CMML). It is estimated that only 5,000 to 6,000 Americans will be diagnosed with this aggressive form of leukemia in the United States in a given year. The new research could eventually help doctors make a better assessment of a patient’s disease, leading to improved therapy. “We are working for the day when patients are treated on a just-in-time, individualized basis, using their individual biomarkers to select the optimal therapy,” said Nello Cristianini, an HMS professor of computer science and of systems biology and co-principal investigator of the program along with Daniel Weinstock, a research scientist at the Broad Institute. To make the research project possible, Cristianini, Weinstock and collaborators at Dana-Farber are harnessing a unique resource called TCGA — The Cancer Genome Atlas — an analysis of more than 10,000 tumors from 33 types of cancer that has been performed by the Broad Institute and the National Cancer Institute. The Broad Institute’s cancer genome teams have joined forces with HMS investigators to use the TCGA data to learn what is different about CMML. “This is one of the few cancers in which the researchers actually know what is different about it, because the samples came from hundreds of patients, so you can compare the genomes and get a very detailed look at what’s going on,” said Cristianini. The Broad/Dana-Farber team plans to identify some 2,000 different patterns of variation, or gene expression, and then test how important those patterns are in causing the disease, by comparing these patterns with patients’ clinical records. Because CMML patients are not as common as, for example, colon cancer patients, a disease with a more typical incidence rate of 20,000 per year, identifying potential drug targets in these patients becomes an important step to improving their care. The Broad Institute team plans to share all of the data in an open-access database, called GenePattern, where researchers around the world will be able to use the data to see which patterns are important. This could be of great interest to pharmaceutical companies and could lead to tests for new therapeutics. As for patients with CMML, their disease is so rare that no studies have yet been done to see how often a patient’s molecular subtype corresponds with the tumor in their bone marrow. Researchers will be able to start addressing this question with the data the project generates. If the clinical correlation studies yield usable data, this information could ultimately enable researchers to produce diagnostic tools and drug discovery tools that would enable physicians to tailor treatment to each patient’s unique biology. “This is also how you find the best drugs for each patient,” said Weinstock. The Broad Institute and Dana-Farber Cancer Institute are in the midst of a $3 million grant from the National Cancer Institute to accelerate research in CMML and other rare cancers. Cristianini and Weinstock are seeking other researchers to participate in the project by contacting them at cncrint@broad.mit.edu. The National Cancer Institute has published a special news release to acknowledge the grant. You can read it here.