It's April, and that can only mean one thing at the NCI. No, it's not the DC Cherry Blossom Festival, but the Annual Meeting of the American Association for Cancer Research (AACR). This year's gathering of oncology-laden minds was inundated with a plethora of multiple symposia, educational and scientific sessions, workshops, talks and poster presentations that revolved around the theme of cancer genomics. The opening plenary session featured the NCI Director, Dr. Harold Varmus emphasizing the importance of defining malignant genomes to provide a foundation to base future cancer research. Appropriately, the NCI Office of Cancer Genomics (OCG) was well-represented throughout the conference, accentuating not only the research programs supported through the office but also the investigators that make OCG initiatives successful. In his talk, Dr. Varmus further alluded to the critical aspect of integrating genomic data discovered for as many cancers as possible, and in particular a select few cancers, which were highlighted in the 2012 NCI Professional Budget JudgmentOpens in a New Tab (also known as the Bypass Budget) "Cancer: Changing the Conversation" as more of an immediate priority for the NCI. While most of the adult cancers listed in the Bypass Budget are currently under investigation by a well-known large-scale genomics initiative piloted in OCG, The Cancer Genome Atlas (TCGA)Opens in a New Tab, two childhood cancers were also included, neuroblastoma and acute myeloid leukemia (AML). Both of these pediatric cancers are currently being studied as part of the current OCG initiative, Therapeutically Applicable Research to Generate Effective Treatments (TARGET)Opens in a New Tab.
TARGETing Cancer Health Disparities
The AACR organized several sessions highlighting TARGETOpens in a New Tab pediatric projects in both neuroblastoma and childhood leukemia. In addition to an NCIOpens in a New Tab/NIHOpens in a New Tab sponsored educational session, which generally informed on the TARGETOpens in a New Tab initiative as a whole, exome and whole genome sequencing efforts of the neuroblastoma project were featured in a major symposium and two minisymposia. Additionally, data from the pilot project for acute lymphoblastic leukemia (ALL) was at the forefront of a pediatric session on new concepts in organ site research, which focused on potential new therapeutic targets specific for the disease. The TARGETOpens in a New Tab ALL project team has already published several interesting papers describing potential drug targets discovered through genomic characterization. Additionally, some TARGET ALL project team members recently reported in Nature GeneticsOpens in a New Tab that pharmacogenomics, the study of genetics as related to drug response, revealed that ancestry alters a child's risk of relapse and survival in certain types of ALL. Specifically, African American and Hispanic ethnicities are associated with poor survival when compared with Caucasian and Asian Americans, and Native American ancestry was found to significantly increase risk of relapse in pediatric ALL. Of great interest is that a single extra phase of chemotherapy reduced the risk of relapse equivalent to that seen among other ethnicities. This finding provides the first validated genomic evidence of a heritable genetic basis for ethnic disparities in cancer survival, and outlines how genomics studies can lead to modifications in therapy that will result in better outcomes for cancer patients.
One area of focus for AACR, NCIOpens in a New Tab and cancer research at large is the issue of health disparities and the need for proper cancer education of underserved populations. The annual AACR meeting is unique in the cancer field, as it draws not only clinicians and scientists that perform cancer research, but also students and trainees at all levels, science and biotechnology industry and pharmaceutical representatives, patient advocates and even cancer patients. Cancer directly affects more than 1 in 3 Americans personally every year, which makes tumor biology education critical among all ages, ethnicities and cultures in the US. For example, the remarkable results obtained in the TARGETOpens in a New Tab ALL pharmacogenomics study previously mentioned are of little benefit if the Native American culture is unable to understand the implications, not only of the outcome but of the necessity of participating in such genomics studies that will lead to more effective treatments for all populations. "Culturally targeted and sensitive cancer outreach and education program activities need to be included in all research focusing on genomics and genetically-targeted medicine and treatments, which include Native Americans and any underserved population. And outreach and education about underserved populations is required of and includes researchers and their staff," notes Phyllis Pettit Nassi, MSW, Manager of Special Populations at Native American Outreach. She and countless other advocates attend AACR to learn about what is being done in cancer research as well as to educate the research and medical community about issues underlying their science. OCG understands the need for and further supports the expansion of cancer genomics education to include people of all ages, ethnicities, cultures and education levels. As cancer research enters an age of the cancer genome and epigenome, it will be important to create a robust infrastructure of information that allows each patient, student, researcher and clinician alike to fully grasp the concepts being studied, the resulting data obtained and how to properly interpret findings so that medicine can be improved.
Translating the Data
A key component in using genomics to better understand and treat cancer is the ability to integrate and interpret the massive amounts of data being generated by large-scale genomics initiatives such as TARGETOpens in a New Tab, TCGAOpens in a New Tab, and the Cancer Genome Characterization Initiative (CGCI). CGCI currently has data available through OCG Data Portals for medulloblastoma and diffuse large B-cell lymphoma (DLBCL), and data from HIV+ cancers and Burkitt's lymphoma projects will be coming in the future. CGCI investigators recently published their findings in ScienceOpens in a New Tab, noting the overall lack of genetic mutations in medulloblastoma versus adult cancers. The investigators also noted that the mutations present largely appear in genes involved in normal developmental processes. Additionally, a promising therapeutic target for DLBCL was presented by a CGCI investigator during a minisymposium at AACR.
As with TARGETOpens in a New Tab and CGCI, another OCG initiative known as the Cancer Target Discovery and Development (CTD2) Network had investigators prominently featured at this year's AACR as well. A major plenary session featured Dr. Andrea Califano discussing the use of systems biology to study integrative cancer genomics, and 3 other major symposia included talks by network colleagues surrounding the need for proper translation of genomics data to be useful in cancer treatment. The CTD2 Network focuses on the development of novel scientific approaches to accelerate the translation of genomic discoveries into new cancer treatments. The network emphasizes interaction of laboratories with complementary and unique expertise, including bioinformatics, genome-wide loss of function screening and targeted gain-of-function candidate gene validations, judicious use of mouse-based screens and small molecule high-throughput screens. The NCI announced its intent to publish a request for applications for CTD2Opens in a New Tab in coming months, which will present a timely opportunity to explore new methods for translation of large-scale genomics; a topic heavily emphasized at AACR and with NCI.
The 102nd Annual AACR Meeting was highly successful in spotlighting all that has been accomplished in the 40 years since the National Cancer Act was signed into law. The title on the AACR meeting program, "Innovation and Collaboration: the Path to Progress", clearly defines the goal for the event in which the theme of cancer genomics was so greatly interwoven. The time for defining the cancer genome is here, and OCG is leading many of the projects taking on that challenge. The OCG pathway of progress will serve to lay the foundation for the next 40 years of cancer innovation by enhancing the understanding of the molecular mechanisms of cancer, advancing and accelerating genomics science and technology development, and efficiently translating the genomics data to improve cancer prevention, early detection, diagnosis and treatment.