Universities bring personalized medicine to the forefront of patient care

Abstract

In personalized medicine, each patient's unique clinical, genetic, and genomic information is used to tailor and customize their treatment. Now, 2 programs are helping to make personalized medicine more accessible to both patients and physicians. Although universities across the country are conducting research in the field, these programs specifically focus on applying personalized medicine knowledge directly to patient care. One of those efforts is “My Cancer Genome,” which was launched by the Vanderbilt-Ingram Cancer Center (VICC) in Nashville, Tennessee, in January 2011. It is billed as the nation's first personalized cancer decision support tool and is designed to help physicians and researchers stay up-to-date on the latest personalized medicine therapies and clinical trials available for patients. “My Cancer Genome” initially was established to help Vanderbilt's clinicians treat their patients, and is linked to their electronic medical records so physicians can immediately recommend treatments and trials during patient visits. Physicians at other institutions also can now search the Web site (available at www.mycancergenome.org) to learn about the rapidly expanding list of genetic mutations related to different cancers and treatment options based on specific mutations. When physicians receive tumor profiling results from a laboratory that indicate a mutation in a specific gene, they then can access the Web site to find the latest clinical implications by reading a summary or by accessing links to primary literature, thereby saving them from having to do an extensive literature search. “The level of information is not always known, and it's always changing,” says Mia Levy, MD, PhD, cancer clinical informatics officer for VICC. It's not always enough to know that a lung cancer patient has an [epidermal growth factor receptor] EGFR mutation, for example. Physicians need to know the specific variant of the gene because some will confer sensitivity to the drug erlotinib, while others actually will be resistant. The site tells physicians how common a particular variant is as well as its sensitivity to specific drugs. The BRAF V600E mutation in patients with metastatic melanoma is one example of a variance that recently was demonstrated to respond well to the BRAF inhibitor vemurafenib. Other variants do not have as much data available at this time. Initially launched with information regarding mutations in lung cancer and melanoma, the site now has content on breast, colon, and thyroid cancers as well as gastrointestinal stromal tumors and thymic carcinoma. Organizers plan to add information concerning hematologic tumors soon. At press time, the content included information regarding approximately 22 different genes and 200 disease gene variants, and the site had had approximately 50,000 unique visits from 117 different countries since the time it was first launched. Because the Web site does not require a login or password, coordinators at VICC do not know precisely who is accessing it; however, informal surveys have indicated that patients have visited the site even though it is designed for a professional medical audience. With time, the creators may develop a version that is geared more toward a lay audience, says Dr. Levy. Because the data are complex and ever-changing, they are gathered from multiple sources. The site relies on 30 contributors from 13 institutions in 6 countries, and that list is continually growing. The site also culls data from more than 12,000 active clinical trials in the National Cancer Institute's Physician Data Query database and filters that list down to those trials that are relevant to patients with specific mutations. “It's important that as clinicians are starting to use the site, they come back each time they're making a new treatment decision for their patient because each time there is new knowledge and new clinical trials that may be available,” Dr. Levy says. “It's not a static report—it's a living Web site that changes all the time.” In addition, scientists at Washington University in St. Louis, Missouri, are offering a new genetics test that will help physicians determine the best treatment for their patients with cancer. The university's genomics and pathology services (GPS) group offers a test for mutations in 27 genes associated with a variety of tumors, including blood, lymph, lung, brain, bladder, kidney, skin, stomach, prostate, and breast cancers. “We do genome-wide sequence analysis on patient specimens to direct patient care now,” says Karen Seibert, PhD, director of the GPS group. “We are not a basic research enterprise. We do clinical testing and clinical research in College of American Pathologists- and Clinical Laboratory Improvement Amendments-certified labs.” Although the testing can be applied to many areas, the group began with oncology because of the many clinical applications that exist, she says. Patients who have received a recent diagnosis of cancer; Patients who have a mutation for which a therapeutic regimen exists; Patients who are actively looking for clinical trials and wish to know more about whether they have a specific genetic mutation; and Patients who have failed standard treatments. Scientists can develop a genetic profile of their cancer, determine which mutations exist and why treatment did not work, and then direct them to appropriate clinical trials. Washington University has conducted clinical genetic testing for many years, but the GPS group launched its new testing using next-generation genetic (next-gen) sequencing in November 2011. “At the end of the day, next-gen sequencing is just another lab test,” says John Pfeifer, MD, PhD, vice chair for clinical affairs in the department of pathology and immunology at Washington University. “But we recognize that it provides an opportunity to do more for patient care than what typically is done now.” The older methods of genetic testing, including Sanger sequencing, are not as sensitive and are much more costly and inefficient if scientists are searching for 3 or 4 genes or multiple mutations rather than just 1, he says. Sanger sequencing has the capacity to examine between hundreds to several thousand bases of sequences, whereas next-gen sequencing can examine millions of bases of sequences. In that way, next-gen sequencing is both broader, enabling scientists to examine panels of a gene at a time, and more precise, enabling them to examine a single base pair and larger chromosomal areas than they can find through cytogenetics and microarray analyses. As a result, the patient will have a shortened and more precise diagnostic experience. “It's our hope that with better genetic information, patients can receive optimal treatments sooner,” says Dr. Seibert. Next-gen sequencing is used extensively in research to better understand diseases and disease processes, but when used as clinical testing for patient care, it requires different validation and a different regulatory environment, says Dr. Pfeifer. Its value within the context of patient care is providing oncologists with information regarding whether patients have specific mutations that can be treated by available drugs. In patients with gastrointestinal stromal tumors, for example, 4 different exons can be mutated in the c-kit gene, and next-gen testing allows scientists to examine all 4 of them in 1 run, Dr. Pfeifer says. That allows them to quickly provide clinicians with the necessary information with which to make treatment decisions. Although the costs of next-gen sequencing are rapidly declining, the technology will not be available in clinical laboratories across the country in the near future because it requires large investments and a large infrastructure to support. Currently, only approximately 20 laboratories across the country offer the next-gen sequencing approach and most are at major academic medical centers, says Dr. Pfeifer. Their laboratory is one of just a few focusing the technology on cancer because the disease is more complicated, with more genes and more patterns of mutation. As a result, the work requires greater expertise in being able to find the mutations. “We need experts to look at, sort out, and interpret the information, which is why this marriage of the geneticist and pathologist is so important to us,” says Dr. Seibert. Dr. Pfeifer adds that the program's strength is their bioinformatics component, which enables them to analyze the billions of base pairs of sequence that are generated and find and interpret mutations that actually are correlated with disease.