Research

OSUCCC – James Leads Statewide Initiative Against Lung Cancer

Recruitment is underway for a statewide clinical research initiative taking aim at lung cancer, the No. 1 cancer killer among men and women in the United States. Led by Peter Shields, MD, David Carbone, MD, PhD, Barbara Andersen, PhD, and Mary Ellen Wewers, RN, PhD, MPH, the initiative is called Beating Lung Cancer – In Ohio (BLC – IO) and is supported by $3 million from Pelotonia, an annual grassroots cycling event that raises money for cancer research at Ohio State. The initiative will draw upon a network of 50 hospitals around Ohio that was established by an earlier statewide project—the Ohio Colorectal Cancer Prevention Initiative—which was also led by the OSUCCC – James and funded by Pelotonia. BLC – IO has two aims: to evaluate the impact of advanced gene testing and expert advice on lung cancer treatment and patient survival; and to improve smoking-cessation rates among smokers with lung cancer and their family members. Patient recruitment began in March 2017 and will extend over a three-year period.

Genomics-Driven Statewide Endometrial Cancer Research Initiative Launched

The OSUCCC – James launched a third statewide clinical cancer research project—the Ohio Prevention and Treatment of Endometrial Cancer (OPTEC) initiative—that is supported by funding from Pelotonia, an annual grassroots cycling event that raises money for cancer research at Ohio State. Building off the community-hospital network that was developed during the OSUCCC – James’ first statewide Pelotonia-funded project (Ohio Colorectal Cancer Prevention Initiative), OPTEC will recruit up to 700 Ohio women with endometrial (uterine) cancer who will be screened for Lynch syndrome (LS) and other inherited genetic conditions linked to greater risk of endometrial, colorectal, stomach and ovarian cancers. Their tumor samples will undergo molecular profiling to identify targeted treatments personalized to each patient’s tumor characteristics. Patients identified with LS and their at-risk family members will be educated about the importance of genetic testing and cancer-prevention strategies based on their increased risk for LS-associated cancers. OPTEC, supported by $1 million in Pelotonia funds, is led by David Cohn, MD, and Paul Goodfellow, PhD, with collaborators from the OSUCCC – James and Nationwide Children’s Research Institute.

Advances Prompt Release of New Recommendations for Diagnosis Management of Adult AML

An international panel of experts released updated evidence-based and expert-opinion-based recommendations for the diagnosis and treatment of acute myeloid leukemia (AML) in adults. The recommendations were issued by the European LeukemiaNet (ELN) and published in the journal Blood. The paper’s senior author was Clara D. Bloomfield, MD, a Distinguished University Professor at Ohio State who also serves as cancer scholar and senior adviser for the OSUCCC – James. Bloomfield, who chaired the panel, says these guidelines are an important update of the current and widely used recommendations for managing patients with AML, for constructing clinical trials and for predicting outcomes of AML patients. The guidelines replaced the 2010 ELN recommendations. Read more

New Prognostic Classification May Help Clinical Decision-Making in Glioblastoma

Research led by scientists at the OSUCCC – James showed that taking molecular variables into account will improve the prognostic classification of the lethal brain cancer called glioblastoma (GBM). Published in the journal JAMA Oncology, the study found that adding significant molecular biomarkers to the existing GBM classification system improves the prognostic classification of GBM patients who have been treated with radiation and the drug temozolomide. Arnab Chakravarti, MD, professor and chair of the Department of Radiation Oncology at Ohio State, was principal investigator. Erica Bell, PhD, a researcher at the OSUCCC – James, was first author. In a separate study, the same team of researchers found that MGMT promoter methylation status—molecular information gathered at a DNA level—can help predict overall survival for patients with a rare brain cancer called anaplastic astrocytoma. MGMT is a DNA repair gene and a biomarker in grade 4 glioblastoma brain tumors. This study, presented at the American Society of Radiation Oncology annual meeting, sought to determine the number of patients with positive MGMT promoter methylation status and its significance in predicting survival outcomes for anaplastic astrocytomas. Read more

2 Investigational Antitumor Agents Work Better Together Against MPNST and Neuroblastoma

Two investigational agents—aurora A kinase inhibitor (alisertib) and HSV1716, a virus derived from HSV-1 and attenuated by the deletion of RL1—have shown some antitumor efficacy in early clinical trials as monotherapies. However, a study published in early 2017 in the journal Oncotarget demonstrated that the combined use of the agents results in significantly increased antitumor efficacy in models of malignant peripheral nerve sheath tumor (MPNST) and neuroblastoma. Researchers investigated this combination in MPNST and neuroblastoma because these difficult-to-treat sarcomas have shown susceptibility to these agents individually. Senior author was Timothy Cripe, MD, PhD, professor of Pediatrics at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James.

Study Reveals How Cancer Cells May Develop Resistance to FGFR Inhibitors

OSUCCC – James researchers identified a mechanism by which cancer cells develop resistance to a class of drugs called fibroblast growth factor receptor (FGFR) inhibitors. Published in the journal Molecular Cancer Therapeutics, their study also found that the use of a second inhibitor may boost the effectiveness of these drugs by preventing resistance; researchers recommend that clinical trials be designed to include a second inhibitor. FGFR inhibitors are a family of targeted agents designed to inhibit the action of the fibroblast growth factor receptor, which is often overexpressed in lung, bladder, biliary and breast cancers. Principal investigator was Sameek Roychowdhury, MD, PhD, assistant professor in the Division of Medical Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James. Read more

Rise in Lung Adenocarcinoma Linked to ‘Light Cigarette’ Use

A study by researchers at the OSUCCC – James and other universities/cancer centers showed that so-called “light” cigarettes have no health benefits to smokers and have likely contributed to the rise of adenocarcinoma, the most common lung cancer. Researchers examined why adenocarcinoma has increased over the years rather than decreased as more smokers have quit. Study results confirmed there is no health benefit to high-ventilation (light) cigarettes—long marketed by the tobacco industry as a “healthier” option—and that these cigarettes have caused more harm. Ventilation holes in cigarette filters were introduced 50 years ago and were critical to claims for low-tar cigarettes. Data suggests a clear relationship between the addition of ventilation holes to cigarettes and increasing rates of lung adenocarcinoma, says Peter Shields, MD, deputy director of the OSUCCC and a lung medical oncologist. Min-Ae Song, PhD, assistant professor in the College of Public Health at Ohio State, was first author on the study. Read more

Researchers Study Strawberries for Fighting Oral Cancer in Heavy Smokers

Can cigarette smoke and the saliva of heavy smokers influence the metabolism of cancer-inhibiting chemicals found in strawberries and the expression of genes associated with oral cancer risk? A pilot study at the OSUCCC – James hypothesized that they can, and initial data revealed some intriguing differences in the oral microenvironment of smokers versus non-smokers. The researchers reported their findings at the American Association for Cancer Research (AACR) 2017 Annual Meeting. Jennifer Ahn-Jarvis, PhD, a postdoctoral fellow in The Ohio State University College of Dentistry, was first author of this multidisciplinary study. Read more

Large AML Study Correlates Gene Mutations with 34 Disease Subgroups

A study of adults with acute myeloid leukemia (AML) correlated 80 cancer-related gene mutations with five subtypes of AML, which are defined by the presence of chromosomal abnormalities. Led by researchers at the OSUCCC – James, the study involved 1,603 newly diagnosed adult AML patients treated on Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology trials in centers across the United States. Researchers combined the cytogenetic abnormalities that define 34 AML subgroups with the mutation status of the 80 cancer-related genes to produce a summary of mutations associated with each cytogenetic group. Ann-Kathrin Eisfeld, MD, of the Internal Medicine/Physician-Scientist Training Program at Ohio State, was first author of the study, published in the journal Leukemia. Clara D. Bloomfield, MD, a Distinguished University Professor who also serves as cancer scholar and senior adviser to the OSUCCC – James, was senior author. Read more

Study Examines Landscape of Genome-Wide Age-Related DNA Methylation in Breast Tissue

Age-related DNA methylation (aDNAm) may be an important pathway for increased cancer risk with age, according to an OSUCCC – James study that provided the first comprehensive report of changes in DNA methylation with age in normal breast tissues of women without a history of breast cancer. DNA methylation is a natural process through which cells deregulate (turn off) unneeded genes. Properly regulated methylation is critical to normal development, but aberrant methylation contributes to cancer by silencing tumor-suppressor genes that normally prevent improper cell division. In this study, breast tissues from a cross-sectional group of https://jamanetwork.com/journals/jamasurgery/article-abstract/2623723121 cancer-free women were examined for genome-wide DNA methylation, and mRNA expression was assayed by microarray technology. Analysis of covariance was used to identify altered methylation at 1,214 aDNAms, almost all of which were increased methylation. Writing in the journal Oncotarget, the researchers say their results are consistent with the hypothesis that the relationship of aging to breast cancer may be explained in part by age-related changes in DNA methylation and gene expression in normal tissues before cancer develops, warranting further study. OSUCCC Deputy Director Peter Shields, MD, was principal investigator. Min-Ae Song, PhD, assistant professor in the College of Public Health, was first author.

Over Half of Breast Cancer Patients Pursue Reconstructive Surgery Without Understanding of Risks

More than half of breast cancer patients (57 percent) undergoing mastectomy lack the medical knowledge to make a high-quality decision about reconstructive surgery that aligns with their personal goals, suggesting a trend toward overtreatment, according to a study at the OSUCCC – James. The study defined “high-quality” decisions as those that demonstrated adequate medical knowledge of treatment choices—including associated risks—and that also matched the patient’s goals and preferences for choosing whether to pursue reconstructive surgery. Researchers reported their findings in the journal JAMA Surgery. Clara Lee, MD, MPP, associate professor in the Department of Plastic Surgery at Ohio State and member of the Cancer Control Program at the OSUCCC – James, was principal investigator. Read more

First Study of Oncolytic HSV-1 in Children and Young Adults with Cancer Indicates Safety and Tolerability

An oncolytic (cancer-killing) herpes simplex virus-1 called HSV1716 has been studied in adults via injection into the brain and superficial tumors. In 2017, a team of researchers at Nationwide Children’s Hospital and Cincinnati Children’s Hospital Medical Center completed the first phase I trial of the virus in the pediatric population, published online in the journal Clinical Cancer Research. Children with relapsed or refractory solid tumors have poor outcomes and significant toxicities from available therapies, so researchers and clinicians are looking to novel treatment strategies, including oncolytic virotherapy. In this phase I study, researchers observed that intratumoral HSV1716 is safe and well-tolerated in children and young adults with late-stage, aggressive cancer. Timothy Cripe, MD, PhD, professor of Pediatrics at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, was senior author on the study. Read more

Digital Pathology Could Improve Accuracy, Timeliness of Cancer Diagnosis

In April 2017 the U.S. Food and Drug Administration approved digital pathology for use in primary cancer diagnosis, opening the door for clinical pathology services to undergo important changes that will make it easier to share cases for expert review and use sophisticated quantitative algorithms to accurately stage and grade cancer. The OSUCCC – James is implementing a long-term digital pathology workflow solution for the cancer program as well as the overall health system at Ohio State. All new patient pathology slides will be digitized along with the past seven years of pathology slides processed at the hospital. The digital pathology service is led by Anil Parwani, MD, PhD, MBA, director of digital pathology and vice chair/director of anatomic pathology in the Department of Pathology at Ohio State. Read more

First-Line Immunotherapy Treatment Can Improve Survival for Subset of Lung Cancer

Findings from a phase III clinical trial for advanced lung cancer patients could help oncologists better predict which patients are likely to receive the most benefit from immunotherapy as a first-line treatment based on the unique molecular characteristics of their tumor, according to a study reported by a global team led by David Carbone, MD, PhD, director of the Thoracic Oncology Center at the OSUCCC – James. Researchers compared the effectiveness of the immunotherapy drug nivolumab with standard-of-care chemotherapy in 541 patients with previously untreated or recurrent non-small cell lung cancer (NSCLC) that expressed PDL-1 antibodies. Patients were randomized to receive either immunotherapy or standard-of-care chemotherapy. Study findings were reported in the New England Journal of Medicine. Read more

Walking Gait & Balance Negatively Impacted After Chemotherapy Treatment

A single chemotherapy treatment can have a negative impact on walking gait and balance, putting patients at an increasing risk for falls, according to a study involving breast cancer patients that was conducted by researchers at the OSUCCC – James. Up to 60 percent of patients experience chemotherapy-induced peripheral neuropathy (CIPN), or nerve damage that impacts feeling in the hands or feet; however, when and to what extent this damage impacts functional abilities has been largely unknown. This study was the first to objectively measure the functional abilities of cancer patients during and after taxane-based chemotherapy. Maryam Lustberg, MD, MPH, associate professor of Medical Oncology at Ohio State and medical director of survivorship at the OSUCCC – James, was senior author of the study, published in the journal Breast Cancer Research and Treatment. Read more

Targeted Therapies Show Initial Effectiveness in Subset of Papillary Thyroid Cancer

Two immunotherapy drugs approved by the U.S. Food and Drug Administration for treating melanoma also show promise for treating a rare but aggressive form of papillary thyroid cancer (PTC). Up to 44 percent of PTC patients have a B-raf gene mutation that can be targeted by cancer drugs. In a randomized, phase II, multicenter clinical study led by Manisha Shah, MD, a professor of Medical Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, investigators tested the effectiveness of the targeted therapy drug dabrafenib given alone and in combination with trametinib to treat a subset of advanced PTC patients with B-raf mutations. Researchers presented their findings at the American Association of Clinical Oncology 2017 annual meeting. Read more

Study Reveals New Mechanism of ‘Natural Killer Cell’ Activation

Researchers discovered a mechanism that enables a certain type of immune cell to recognize and kill viral-infected cells. Findings from the multi-institutional study, led by scientists at the OSUCCC – James, could have important implications for vaccines against infectious diseases, understanding and treating autoimmune diseases, preventing some infusion reactions and improving immune therapy for cancer. Published in the journal Immunity, the study focuses on immune cells called natural killer (NK) cells. It identified a previously unknown role of the lower half of an antibody called immunoglobulin G (found on NK cells) in immune responses, opening possibilities for its involvement in cancer immunotherapy. HongSheng Dai, PhD, a research scientist at the OSUCCC – James, was first author and co-corresponding author. Former OSUCCC Director and James CEO Michael A. Caligiuri, MD, was principal investigator. Read more

Researchers Validate Clinical Test for Fusion Genes

An assay that identifies an abnormality in cancer cells has been developed and validated by researchers at the OSUCCC – James. Known as OSU-SpARKFuse (Ohio State University-Spanning Actionable RNA Kinase Fusions), the assay detects a genetic change called gene fusions in solid tumors. The assay and its validation were published in the Journal of Molecular Diagnostics. Gene fusions occur when parts of two different genes join, possibly becoming a driver of cancer-cell and tumor growth. Whereas current methods for detecting fusions require previous knowledge of both genes involved, OSU-SpARKFuse detects fusions when only one of the genes is known, allowing for discovery of novel fusions. Sameek Roychowdhury, MD, PhD, assistant professor of Medical Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, was principal investigator. Read more

Study Identifies miR122 Target Sites in Liver Cancer and Links a Gene to Patient Survival

A study of a molecule that regulates liver cell metabolism and suppresses liver cancer development showed that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, as often happens during liver cancer development, the activity of certain cancer-promoting genes goes up. The findings could help doctors better predict survival in liver cancer patients and determine whether the molecule—microRNA-122 (miR-122)—should be developed as an anticancer drug. Reported in the journal Molecular Cell, the study was led by researchers at the OSUCCC – James and at Rockefeller University’s Howard Hughes Medical Institute. Co-principal investigator was Kalpana Ghoshal, PhD, associate professor of Pathology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James. Read more

Long-Term, High-Dose B6-B12 Use Associated With Increased Lung Cancer Risk Among Men

Research suggests long-term, high-dose supplementation with vitamins B6 and B12—long touted by the vitamin industry for increasing energy and improving metabolism—is associated with a two- to four-fold increased lung cancer risk in men relative to non-users. Risk was further elevated in male smokers taking more than 20 milligrams of B6 or 55 micrograms of B12 a day for 10 years. Epidemiologists from the OSUCCC – James, Fred Hutchinson Cancer Research Center and National Taiwan University reported the findings in the Journal of Clinical Oncology. For this study, Theodore Brasky, PhD, research assistant professor and member of the Cancer Control Program at the OSUCCC – James, and colleagues analyzed data from more than 77,000 patient participants in the VITamins And Lifestyle (VITAL) cohort study. Read more

Onalespib Could be Effective Treatment for Glioblastoma

The targeted therapy onalespib has shown effectiveness in preclinical studies of glioblastoma by OSUCCC – James researchers. Onalespib inhibits a molecule called HSP90 that helps newly made protein molecules fold into their final functional form. Many receptor and DNA-damage-response proteins require HSP90 to achieve their functional conformation. In cancer cells, HSP90 can be expressed up to 10 times higher than in normal cells. In this study, onalespib blocked HSP90 activity and reduced the expression of cell-survival proteins such as AKT and endothelial growth factor receptor in glioma cell lines and in glioma stem cells obtained from patient tumors. This reduced the survival and proliferation of the cells. Findings appeared in the journal Clinical Cancer Research. Vinay Puduvalli, MD, professor and director of the Division of Neuro-Oncology at Ohio State and member of the OSUCCC – James, was principal investigator. Read more

CAR-T Immunotherapy Approved for Certain Lymphoma Patients

The U.S. Food and Drug Administration (FDA) has approved a breakthrough cancer therapy known as CAR-T for use in adults with advanced lymphoma. The therapy, which was also approved for a rare type of treatment-resistant childhood leukemia, uses a patient’s white blood cells, which are modified in a lab and re-trained to recognize specific biomarkers on the surface of the cell, and then to target and kill only those cancerous cells. Samantha Jaglowski, MD, MPH, assistant professor of Hematology at Ohio State and member of the Leukemia Research Program at the OSUCCC – James, tested the therapy in clinical trials and describes this as truly a “living therapy”: A patient’s own cells being reinfused and set to work fighting cancer, a prime example of personalized medicine. The OSUCCC – James was the first cancer center in Ohio to offer CAR-T therapy and is the only Ohio center approved to administer it with two drugs, Yescarta and Kymriah. Cleveland Clinic is approved for using Yescarta; Nationwide Children’s Hospital and Cincinnati Children’s Hospital Medical Center are approved for using Kymriah. Clinical trials are available at all four locations, as well as Case Western Reserve University. Read more

OSUCCC – James Researchers Report on Advances in CLL Treatment at ASH

At the 2017 annual meeting of the American Society of Hematology (ASH), OSUCCC – James scientists reported on advances in the treatment of chronic lymphocytic leukemia (CLL) involving the drug acalabrutinib as a single agent and in dual- and triple-agent combinations. Acalabrutinib is a second-generation
Bruton’s tyrosine kinase (BTK) inhibitor, a newer class of drugs shown to improve the survival of patients with CLL and mantle cell lymphoma. All preclinical research and the first phase I study of the drug were completed by researchers led by John C. Byrd, MD, Distinguished University Professor at Ohio State and co-leader of the Leukemia Research Program at the OSUCCC – James. Studies involving acalabrutinib in dual- and triple-agent combinations at Ohio State were led by Jennifer Woyach, MD, and Kerry Rogers, MD, assistant professors of Hematology and members of the Leukemia Research Program.

Researchers Turn to Technology to Improve Bladder Cancer Identification

Accurately calculating the stage of bladder cancer in a patient is vital in determining treatment options. If the cancer has spread deep into the four layers of the bladder, then a radical cystectomy (bladder removal) may be the best option. If it is still in the early stages, a less invasive treatment with fewer long-term side effects could be used. Inadequate staging of bladder cancer has long been a problem, but Cheryl Lee, MD, professor and chair of the Department of Urology at Ohio State and a bladder cancer expert at the OSUCCC – James, and colleagues, along with members of the Department of Biomedical Informatics, will utilize digital pathology and advanced computer analytics to better analyze tissue samples from a patient’s bladder cancer and more accurately determine the stage of the cancer. Read more