2014 Saw New Cancer Hospital & Research Advances at Ohio State For Ohio State’s cancer program, 2014 was a pivotal year that culminated in the opening of the new Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, a 21-story, 306-bed facility that stands as a model for 21st century cancer hospitals. The new James, the third largest cancer hospital in the nation, integrates cancer research, patient care and education more closely than ever so that scientific discoveries can be quickly translated to innovative patient care. The extensive preparations for opening and occupying the new hospital, which replaces the original James that opened here in 1990, did not slow the progress of groundbreaking cancer research at Ohio State. Here are some of the many important research achievements by Ohio State medical scientists during 2014: OHIO STATE RESEARCH PLAYS SIGNIFICANT ROLE IN FDA APPROVAL OF CLL DRUG On Feb. 12, the U.S. Food and Drug Administration expanded the approved use of the drug ibrutinib(Imbruvica®) to treat certain patients with chronic lymphocytic leukemia (CLL). Ibrutinib is the first drug designed to target a protein that is essential for CLL-cell survival and proliferation. Much of the clinical and basic-science research that led to FDA approval was performed by scientists at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James), particularly by John C. Byrd, MD, and colleagues Amy Johnson, PhD, Jason Dubovsky, PhD,Jeffrey Jones, MD, MPH, Joseph Flynn, DO, MPH, Jennifer Woyach, MD, Kami Maddocks, MD, and Kristie Blum, MD. Read more STUDY IDENTIFIES LIKELY DRIVER OF COLORECTAL CANCER DEVELOPMENT, PROGRESSION New targets are needed in order to develop drugs that will more effectively treat colorectal cancer (CRC). A study by OSUCCC – James researchers identified a molecule called microRNA-135b that is a likely driver of CRC. Their findings strongly suggest that this molecule could be an important therapeutic target and a valuable biomarker of CRC tumor progression. The study, led by Carlo Croce, MD, was published in the journal Cancer Cell. NEW BIOMARKER FOUND FOR OLDER PATIENTS WITH ACUTE LEUKEMIA Older patients with acute myeloid leukemia (AML) have worse outcomes than younger patients. In about half of these cases, the safest and most effective treatment is difficult to determine. But researchers at the OSUCCC – James described a new biomarker, based on patterns of molecules called long noncoding RNAs, that might help doctors choose the least toxic, most effective treatment for older patients. The study, led by Clara D. Bloomfield, MD, and Ramiro Garzon, MD, was published online in the journal Proceedings of the National Academy of Sciences. Read more STUDIES SHOW POTENTIAL FOR TARGETED THERAPY IN LUNG CANCER PATIENTS OSUCCC – James researchers led by David Carbone, MD, PhD, conducted studies that could improve therapy for patients with lung cancer. A study published in the Journal of Clinical Investigation examined the gene changes in a patient on a clinical trial who responded especially well to an experimental targeted drug called sorafenib. This “super responder” remained progression-free and asymptomatic for five years while taking the drug. The study suggests that scientists can discover gene mutations that drive cancer development and progression by analyzing genes in cancer cells from patients who fare far better or worse than others in a particular study. A second study, published in the journal Cancer Research, focused on the targeted drug erlotinib. This drug is effective in treating advanced-stage lung cancer patients whose tumors have a particular gene mutation, but it is of little or no help to patients with early-stage tumors and the same gene mutation. The study discovered why this might be so, and it suggested that the problem may be solved by combining erlotinib with a second drug. OSU RESEARCHERS DEVELOP ANTICANCER PEPTIDE VACCINES Researchers have developed two anticancer peptide vaccines and two peptide inhibitors as part of a larger peptide immunotherapy effort at the OSUCCC – James. The peptide vaccines and inhibitors are designed to treat cancers of the breast, pancreas, esophagus and colon. Findings from these studies, which were led by Pravin Kaumaya, PhD, also suggest that combining two peptide agents can boost their effectiveness and might help prevent or overcome drug resistance. Read more GENE WITHIN A GENE CONTRIBUTES TO AML AGGRESSIVENESS A small gene that is embedded in a larger, well-known gene is the true leukemia-promoting force usually attributed to the larger host gene, OSUCCC – James researchers learned in a study published in the journal Science Signaling. The study examined the degree to which the larger host gene, BAALC, and the smaller embedded gene, microRNA-3151, contribute to acute myeloid leukemia (AML). It also identified a drug that might inhibit the smaller gene’s activity. The study was led by Albert de la Chapelle, MD, PhD, Clara D. Bloomfield, MD, and Ann-Kathrin Eisfeld, MD. Read more SURVIVAL MOLECULE HELPS CANCER CELLS HIDE FROM IMMUNE SYSTEM A molecule that helps cancer cells evade naturally programmed self-destruction, an internal source of death, might also help malignant cells hide from the immune system, an external source of death. An OSUCCC – James study led by Denis Guttridge, PhD, showed that a molecule called nuclear factor kappa B (NF-kB) helps cancer cells by suppressing the immune system’s ability to detect and destroy them. Published in the journal Cell Reports, the findings suggest that immune therapy for cancer might be more effective if combined with drugs that inhibit NF-kB. They also provide details about how interactions between cancer cells and non-cancer cells assist tumor growth. Read more LOW DOSE OF TARGETED DRUG MIGHT IMPROVE CANCER-KILLING VIRUS THERAPY Viruses designed to kill cancer cells are being used in clinical trials to treat brain cancer and other malignancies. A study led by Balveen Kaur, PhD, at the OSUCCC – James suggested that combining a targeted agent called bortezomib with a particular cancer-killing virus might significantly improve the virus’s ability to kill cancer cells.  The research, published in the journal Clinical Cancer Research, paves the way for a cancer treatment strategy that combines low doses of bortezomib with a cancer-killing virus to maximize the effectiveness of the virus with little added toxicity for patients. FORM OF IMMUNE THERAPY MIGHT BE EFFECTIVE FOR MULTIPLE MYELOMA New treatments are urgently needed for patients with multiple myeloma (MM), a cancer of the blood that is still incurable. An OSUCCC – James study led by Jianhua Hua, PhD, and Craig Hofmeister, MD, provided evidence that genetically altered immune cells might effectively treat MM. The researchers modified a type of human immune cell called T lymphocytes, or T cells, to target a molecule called CS1, which is found on more than 95 percent of myeloma cells, and to kill the cells. Their findings, published in the journal Clinical Cancer Research, presented a novel strategy for treating MM, and they hope to bring it to patients in a phase I clinical trial soon. Read more MECHANISMS OF IBRUTINIB RESISTANCE IDENTIFIED IN CHRONIC LEUKEMIA Ibrutinib is a new and highly effective drug for treating certain patients with chronic lymphocytic leukemia, or CLL (see related item above), but in some cases CLL becomes resistant to this drug, rendering it ineffective. A study at the OSUCCC – James described two genetic mechanisms of ibrutinib resistance in CLL. The researchers, led by John C. Byrd, MD, Amy Johnson, PhD, and Jennifer Woyach, MD, say that knowledge of these mechanisms is the first step toward developing drugs or drug combinations to prevent or treat ibrutinib-resistant CLL. Their study was published in the New England Journal of Medicine. Read more