Study Reveals How Normal Cells Fuel Tumor Growth
A study led by researchers at the OSUCCC – James and published in the journal Nature Cell Biology discovered how normal cells in tumors can fuel tumor growth. The study examined what happens when normal cells known as fibroblasts in mouse mammary tumors lose the PTEN tumor-suppressor gene. The findings suggest new strategies for controlling tumor growth by developing drugs that disrupt communication between tumor cells and normal cells within the tumor. Co-principal investigators Michael Ostrowski, PhD, and Gustavo Leone, PhD, say the study is the first to define a pathway in tumor fibroblasts that reprograms gene activity and the behavior of multiple cell types in the tumor microenvironment, including tumor cells themselves.
Oral HPV Infection 3 Times More Common in Men Than Women
An OSUCCC – James study showed that men are three times more likely to have an oral human papillomavirus (HPV) infection than women – findings that helped explain why HPV-related oral cancers are three times more common in men than women. Maura Gillison, MD, PhD, a medical oncologist and head and neck cancer specialist at the OSUCCC – James, led the study, which was published in the Journal of the American Medical Association to coincide with her presentation of the findings at the Multidisciplinary Head and Neck Cancer Symposium in Phoenix, Ariz. Gillison and collaborators sought to determine the prevalence of oral HPV infection in the United States and understand factors associated with this infection and oropharyngeal cancer.
Beyond the Thymus: Tonsils Make T Cells Too
Research led by scientists at the OSUCCC – James provided evidence that immune cells called T lymphocytes (T cells) can develop in human tonsils. These cells had been thought to develop only in the thymus, an immune system organ. This study, published in the Journal of Clinical Investigation, could improve understanding of T-cell cancers, autoimmune diseases and how stem-cell transplantation is done. “We’ve long known that a functional thymus is necessary to develop a complete repertoire of T cells, but whether a T-cell factory existed outside the thymus has been controversial,” says principal investigator Michael A. Caligiuri, MD. “Our study is the first to describe a comprehensive, stepwise model for T-cell development outside the thymus.”
Mutation Signals High Recurrence Risk in Older AML Patients
Older people with acute myeloid leukemia (AML) and normal-looking chromosomes in their cancer cells have a higher risk of recurrence if they have mutations in a gene called ASXL1, according to a study by OSUCCC – James researchers. The study, published in the journal Blood, was the first to investigate the influence of these mutations on prognosis in patients with cytogenetically normal AML (CN-AML) and in conjunction with other prognostic gene mutations. It also reported the first gene-expression signature for CN-AML with mutated ASXL1. “Our findings could lead to more effective targeted therapies and improved cure rates,” says principal investigator Clara D. Bloomfield, MD, a Distinguished University Professor who serves as cancer scholar and senior adviser to the OSUCCC – James.
Revised Glioblastoma Classification Should Improve Patient Care
Radiation oncology researchers have revised the prognostic model used by doctors since the 1990s for glioblastoma, the most devastating of malignant brain tumors. The previous system was devised for malignant glioma patients who were treated by radiation therapy only, relying on histopathology and clinical variables. The new system accommodates advances in treatment – particularly the use of radiation therapy plus the chemotherapy drug temozolomide – and it incorporates molecular biomarkers as well as clinical variables. Arnab Chakravarti, MD, the study’s national chair for translational research and co-leader of the brain tumor program at the OSUCCC – James, says the new model is more relevant and should better identify patients requiring the most aggressive therapy.
Surgeons Pioneer Removal of Skull Base Tumors Through Nose and Mouth
Surgeons at the OSUCCC – James Cranial Base Center developed a minimally invasive technique to reach and remove skull base tumors through the nose or mouth, sparing patients considerable pain from traditional open surgery and allowing for quicker recovery. The procedure combines endoscopic endonasal surgery with minimally invasive robotic surgery to treat many tumors that are difficult to reach, including some previously considered inoperable. The endoscopic endonasal approach gives surgeons access to the base of the skull, intracranial cavity and top of the spine by operating through the nose and paranasal sinuses. The surgical team includes Ricardo Carrau, MD, Daniel Prevedello, MD, and Enver Ozer, MD.
Study Reveals Mechanism of Lung Cancer Drug Resistance
Research published in the journal Nature Medicine indicated that targeted drugs such as gefitinib might better treat non-small-cell lung cancer if they are combined with agents that block certain microRNAs. The OSUCCC – James study, led by principal investigator Carlo Croce, MD, showed that overexpression of the MET and EGFR genes causes the deregulation of six microRNAs, leading to gefitinib resistance. Findings support the development of agents that restore the levels of these microRNAs, offering a new strategy for treating this disease. The study also suggested that measuring expression levels of certain microRNAs – those controlled by the MET gene – might predict which lung-cancer cases are likely to resist gefitinib.
Possible Therapy Identified for Tamoxifen-Resistant Breast Cancer
A study that discovered how tamoxifen-resistant breast-cancer cells grow and proliferate also suggested that an experimental agent called vismodegib may offer a targeted therapy for patients with this cancer. The study, published in the journal Cancer Research, showed that a signaling pathway called hedgehog (Hhg) can promote breast cancer cell growth after tamoxifen shuts down the pathway activated by the hormone estrogen, and that a second signaling pathway, called PI3K/AKT, is also involved. Researchers led by principal investigator Sarmila Majumder, PhD, and Bhuvaneswari Ramaswamy, MD, say activation of the Hhg pathway makes tamoxifen treatment ineffective, enabling the tumor to resume progression. They analyzed more than 300 human tumors and found that those with an activated Hhg pathway had a worse prognosis.
Scientists Discover Switch That Turns White Fat Brown
OSUCCC – James scientists discovered a biological switch that gives energy-storing white fat the characteristics of energy-burning brown fat. The findings could lead to new strategies for treating obesity, a risk factor for cancer. The animal study, published in the journal Cell Metabolism, showed that the change stems from activation of a nerve and biochemical pathway that begins in the hypothalamus, an area of the brain involved in energy balance, and ends in white fat cells. “One of the holy grails of obesity therapy is to understand how to switch white fat to brown fat; this study describes a way to do that,” says study leader Matthew During, MD, PhD. “Our findings suggest we can induce this transformation by modifying our lifestyle or pharmacologically activating this brain-fat pathway.”
Researchers Identify ‘Life-and-Death’ Molecule on Chronic Leukemia Cells
A study at the OSUCCC – James identified a life-and-death signaling role for a molecule on the surface of the immune cells involved in chronic lymphocytic leukemia (CLL), a finding that could lead to more effective therapy for this incurable cancer. The study, published in the journal Cancer Cell, examined how a drug called SMIP-016 kills CLL cells. Earlier work by these scientists showed that the drug targets a molecule called CD37 on CLL cells. The newer study found that the CD37 molecule has two regions that concurrently activate two pathways in CLL cells, one leading to cell death and another promoting cell survival. Principal investigator (PI) John C. Byrd, MD, says the findings showed SMIP-016 activates the “death” part of the molecule, which suggests that blocking the “survival” part could improve the drug’s effectiveness. Co-PIs for the study are Michael Freitas, PhD, and Natarajan Muthusamy, DVM, PhD.
OSU, Malaysia Centre Join Forces to Develop Anticancer Drug
Ohio State has signed an agreement with the Sarawak Biodiversity Centre in Malaysia to collaborate on further development and commercialization of a promising anticancer agent derived from a tropical tree that grows in the Malaysian state of Sarawak. Researchers with Ohio State’s College of Pharmacy and the OSUCCC – James have worked on the agent, called silvestrol, since 2004. Their early studies indicated silvestrol might help treat acute and chronic leukemia, mantle cell lymphoma and other incurable malignancies. “We will be working with the National Cancer Institute to isolate and purify the agent, and conduct the laboratory and animal studies needed to demonstrate its safety and effectiveness,” says Michael Grever, MD, co-leader of the Experimental Therapeutics Program at the OSUCCC. A. Douglas Kinghorn, PhD, DSc, of the College of Pharmacy, led the work that characterized the molecular structure of silvestrol.
OSU Leads International Pancreatic Cancer Treatment Development Effort
The OSUCCC – James is leading an international pancreatic cancer research effort in collaboration with scientific investigators based in Taiwan and Germany to develop new targeted therapies and biomarkers for pancreatic cancer. Tanios Bekaii-Saab, MD, section chief for gastrointestinal oncology at the OSUCCC – James, and Cheng-Shih Chen, PhD, of the Molecular Carcinogenesis and Chemoprevention Program at the OSUCCC – James, are partnering with doctors at National Cheng-Kung University in Tainan City, Taiwan, and with researchers at the German Cancer Research Center in Heidelberg, to conduct the initiative. The researchers will work to identify new targets in pancreatic tumors and develop novel agents to strike those targets and halt the progression of this disease, for which the overall five-year survival rate is only 5.8 percent.