FIELD NOTES. Chris Anderson our Senior Editor gives a roundup of the recent developments in the precision medicine field.

Transcription

1 FIELD NOTES Chris Anderson our Senior Editor gives a roundup of the recent developments in the precision medicine field.

2 QIAGEN on behalf of the Allele Frequency community Adding value to allele data REDWOOD CITY, Calif. In late winter at the Advances in Genome Biology and Technology (AGBT) scientific meeting in Marco Island, Fla., a coalition of 13 life science and diagnostics companies announced the formation of the Allele Frequency Community, a data gathering and sharing initiative formed to improve the interpretation of sequencing data in both clinical and research settings. community. By combining data from many organizations, we can get far more sensitive measurements of allele frequencies. It s something we can only do together. By pooling the data and making it available from one source, clinicians stand to gain insight into the significance of particular alleles and help them better determine how common some variations are within a population, which in turn helps them distinguish rare, disease-causing variants from more common variations. Researchers can use this information to get a reasonable sense of the allele frequency in a population and perhaps quickly eliminate variants that are common One of the key challenges confronting precision medicine today is context, explained Dr. Doug Bassett, Vice President Translational Research and Chief Scientific Officer at QIAGEN Bioinformatics, which is providing the secure hosting for the data. When interpreting the human genome, you want to know as much about the variants in that genome as possible, including whether any have been associated with disease or simple elements like how common they are. Understanding this can help guide treatment and suggest new areas of disease research. To encourage growth of the resource, users can choose to opt-in to the community. As 7 FIELD NOTES To launch the community, the organizations in ethnic populations that may be underrepre- a condition of opting in, new members agree agreed to pool their extensive exome- and sented in existing public databases, added Dr. to contribute information from their sequences genome-wide variant call data sets in an Heidi Rehm, PhD, director of the laboratory to the community resource. To protect patient anonymized, pooled fashion to create the most for molecular medicine at Partners Healthcare privacy, only anonymous, pooled allele ethnically diverse, freely-accessible, database Personalized Medicine. frequencies are provided. A global resource, of allele frequencies currently available. Allele frequency has become increasingly important tool to help in the interpretation of human variation, but diagnostic labs and clinicians have been hampered by access to limited datasets on allele frequency within a population. At the time of its formation, the Allele Frequency Community database held more than 70,000 variant call data sets, spanning more than 100 countries of origin and 8,000 whole genomes. In the few shorts months since its founding, new members to the Bassett said they are hopeful that the community can add allele information from ethnic populations that are currently underrepresented in public databases, noting that most of that data skews toward North American and European populations. Getting to the population sizes needed to community have increase that number to more For more information on the Allele Frequency define the allele frequencies of rare variants than 100,000 call sets. An internal benchmarking Community and how to participate visit is something individual labs, institutions, or study showed that using the original data commercial entities can rarely achieve on sets provided a 43 percent reduction in false their own, said Jay Shendure, associate positive rates in causal variant identification, professor of genome sciences at the University rates that should continue to improve as more of Washington, a founding member of the variant call data sets are added.

3 Cancer cartographers A broad collaboration between researchers from the University of California, San Diego School of Medicine and University of California, San Francisco announced earlier this year aims to take a big data approach to creating a map of cellular action to gain an understanding of how genetic mutations give rise to cancer. Called the Cancer Cell Map Initiative (CCMI), the broad collaboration intends to provide context to the ever-growing body of information of which genetic mutations are present in cancer and how these mutations affect cell function. Eyes on exceptional responders Massachusetts-based Foundation Medicine announced it will collaborate with the National Cancer Institute on the Exceptional Responder Initiative (ERI), a pilot study that seeks to understand the reasons behind exceptional responses to cancer treatment. Along with other ERI participants Baylor College of Medicine and Nationwide Children s Hospital, researchers will analyze tumor samples collected before initiation of therapy and other pertinent clinical data for more than 300 cancer patients identified as exceptional responders defined as are patients who have experienced an unexpected and durable response to a systemic anti-cancer treatment. The ERI marks the first effort to systematically discover why some patients experience unexpected prolonged responses to therapy following certain treatments. The hope is that information discovered by the ERI will increase the genomic and biologic understanding of cancer, which could ultimately lead to new targeted therapeutics and improve care for a greater number of cancer patients. We are focused on understanding the unique molecular changes that contribute to a patient s individual disease to inform treatment decisions, said Vincent Miller, MD, chief medical officer of Foundation Medicine in a prepared statement. The ERI represents a significant opportunity to utilize advances in precision medicine to better understand outcomes, which can be applied to the future selection of treatments for patients with cancer. The key to understanding genomic information is being able to place it into biological context, said Nevan Krogan, PhD, co-director of CCMI, director of the UC San Francisco division of QB3, and an investigator at the Gladstone Institutes. Mutations in tumor DNA that at first appear to be unrelated may in fact be clustered in specific pathways or multi-protein machines in the cell. The information, in context, will point to areas that we can target with specific therapies. While advances in genome sequencing have identified hundred of specific genetic mutations present in patient tumors, answers about how these mutations give rise to cancer remain elusive. One answer researchers hope to find is why genetic mutations of patients presenting with the same cancer differ greatly from patient to patient. Current thinking is that despite the unique combinations of mutations exhibited by patients, the mutations disrupt the same pathways and genetic circuits. According to CCMI co-director Trey Ideker, PhD, chief of medical genetics in the UC San Diego Department of Medicine and founder of the UC San Diego Center for Computational Biology & Bioinformatics, a current bottleneck is exactly how to interpret cancer genomes. Developing a map of cancer cells and how they become cancerous is the next step in helping to develop more personalized cancer treatments. To get these answers, CCMI will combine UCSD s expertise in biomedical big data with recent advances by UCSF researchers of interrogating the structure and function of cells. Tissue samples for the initiative are being provided by UC San Diego Moores Cancer Center and the UCSF Helen Diller Family Comprehensive Cancer Center. CCMI will also provide support to a collaboration announced last year between Moores and Human Longevity Inc., to sequence the cancer genomes of its patients. Additional information will come from the National Cancer Institute including the cancer genomes and pathways database currently being developed in collaboration with the San Diego Supercomputer Center and UC Santa Cruz.

4 New breast cancer gene IDed Precision s value play A team of Canadian and Polish In a nod to the growing researchers have identified a new influence of healthcare payers breast cancer gene that is strongly in the personalized medicine arena, specialty linked to the onset of the disease. services company Precision for Medicine The study, published online in late announced in mid-april it purchased health April in Nature Genetics details how economics and analytics consultancy Precision Health Economics mutations in the gene RECQL are (PHE) for an undisclosed sum. strongly linked to the onset of breast cancer in two populations of Canadian The acquisition will help Precision for Medicine expand the and Polish women. health economics and outcomes research (HEOR) it currently offers to life sciences clients through its Precision for Value The study was led by Dr. Mohammad business unit. Adding PHE s differentiated capabilities Akbari of Toronto s Women s College fortifies our approach to helping life sciences companies Hospital in collaboration with researchers at deliver more effective treatments to patients in the era Pomeranian Medical University in Poland and Dr. of precision medicine by integrating research, analytics, William Foulkes at McGill University. The Toronto and Polish groups are science, and communications, noted Ethan Leder, longstanding research collaborators. chairman, Precision for Medicine, in an announcement of the deal. The discovery of the RECQL gene link to increased risk of breast cancer marks the first such discovery in eight years. Currently, heredity is the cause Founded in 2005 by University of Southern California of approximately 10 percent of all newly diagnosed cases of breast cancer, with and the University of Chicago professors Dana mutations in the BRCA1 and BRCA2 genes the most common culprits. Women Goldman, Darius Lakdawalla, and Tomas Philipson, with BRCA1 mutations have a 55 percent to 65 percent chance of developing the PHE has developed a network of scholars in the disease, while the risk of those with BRCA2 mutations is around 45 percent. fields of health economics, medicine, and health policy, aimed at helping companies derive value The researchers studied around 20,000 different genes of 195 breast cancer from their scientific IP and determine how public patients with strong family histories of breast cancer, who did not have a mutation policy impacts their markets. in BRCA1 or BRCA2. The patients came from two very homogenous populations: one French Canadian and the other Polish. Within the Polish group, one type of In the age of personalized medicine, it s RECQL mutation showed a five-fold increased risk for developing breast cancer vitally important to understand not only how compared to individuals without a mutation. Meanwhile, within the French-Canadian value derives from tailored treatment, but population, another type of RECQL mutation occurred 50 times more frequently also how to navigate the data, analytics, and among familial breast cancer patients, compared to population controls. policy challenges associated with precision 9 FIELD NOTES This study showed that studying specific founder populations like Polish and French-Canadian women is an excellent approach for identifying disease-associated genes, said Dr. Steven Narod, a senior researcher with Women s College Hospital. The study noted that though the RECQL mutations were relatively rare, there was a high penetrance of the disease about 50 percent of woman with the mutation are expected to develop the disease. The researchers indicate they expect populations of women from other countries will be studied in the near future. medicine. This combination of PHE and (Precision for Medicine) is uniquely suited to meet these challenges, said Goldman. The PHE management team will be retained and will continue to operate from its headquarters in Los Angeles.

5 A new hope for pancreatic cancer BOSTON It s a sad fact that most people diagnosed with pancreatic cancer feel their situation is hopeless. According to the National Cancer Institute, nearly 47,000 Americans were diagnosed with pancreatic cancer last year with a projected five-year survival rate of 6.7 percent. Further, because pancreatic cancer is often diagnosed at such a late stage, as many as 70 percent of newly diagnosed patients, including those with even the smallest tumors forego potential life saving treatments. But the future may be significantly brighter for these patients. A new research collaboration between pharmaceutical company Berg, the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) and the Pancreatic Cancer Research Team (PCRT) managed by Cancer Research And Biostatistics (CRAB), announced it will work to identify biomarkers that can help doctors develop treatment plans for individual patients based on which treatment options are best, and bring a truly targeted approach to fighting pancreatic cancer where none has existed before. Although pancreatic cancer would seem to be a hopeless disease, from those of us who actually work with it, we know otherwise, said A. James Moser, MD, director of the research team for Beth Israel s new Pancreas and Liver Institute and an associate professor of surgery at Harvard Medical School. We know that there are patients who have very indolent forms of metastatic pancreatic cancer. We have patients that shouldn t be cured that are cured. And with the overall survival unfortunately being so short, any biomarker signature might be actionable at a clinical level very quickly. Dubbed Project Survival, the groups involved bring significant capabilities to the collaboration. Berg, which first suggested the partnership in a smaller-scale aimed at developing a pancreatic diagnostic, was easily convinced to enter into a broader collaboration. It brings its Interrogative Biology platform, which takes a machine learning approach to systems biology and can serve as a discovery engine, as well as potentially providing clinical decision support to doctors. The fundamental thing about Berg, is we want to go back to look at individual patients, by phenotype, to understand why patients diagnosed in the same manner have such different outcomes, said Niven R. Narain co-founder, president and chief technology officer of Berg. What is allowing us to get this done is artificial intelligence to make sense of data and to create models that currently don t exist. This partnership is taking a true precision medicine approach to understand and treat pancreatic cancer. PCRT s sole focus is pancreatic cancer and it brings to the table some of the world s leading researchers in the field as well as an international network of 48 cancer centers. Further, PCRT has conducted clinical trials, has experience in FDA registration and, along with BIDMC, has received a grant to establish a bio repository for pancreatic cancer research. Together, the two organizations will design clinical trials and provide both healthy and treated pancreatic tissue, bio-fluids, and treatment results from patients to Berg to analyze. We were already, ready, willing and scientifically able to make this happen from day one, Moser noted. In the short term, Moser hopes the collaboration can bring precision medicine to the treatment of pancreatic cancer that clinicians have available for other forms of cancer. We do have some therapies currently that work, but the problem is the trial and error selection process under which they are applied, he said. I think the short-term view should be can we use precision medicine to identify patients that can respond and will respond to existing therapies today, to help them. Then, long-term, use those wins to understand what the new therapies should look like.