Research

Pelotonia-Funded Study Suggests Many Early-Onset Colon Cancers Are Caused by Genetic Mutations Passed Through Families

One in every six colorectal cancer patients (16 percent) diagnosed under age 50 has at least one inherited genetic mutation that increases cancer risk, and many of these mutations could go undetected with the current screening approach, according to initial data from a statewide colorectal cancer screening study conducted at the OSUCCC – James.

In this new analysis, published in the Dec. 15, 2016, issue of the journal JAMA Oncology, the OSUCCC – James team offers the first detailed report of the prevalence and spectrum of specific mutations in 25 genes associated with inherited cancer syndromes in an unselected series of colorectal cancer patients.

The study includes data from 450 patients with early-onset colorectal cancer who were recruited from a network of Ohio hospitals that was established via the Ohio Colorectal Cancer Prevention Initiative (OCCPI), a statewide study aimed at screening all newly diagnosed colorectal cancer patients in Ohio for Lynch syndrome and other hereditary cancer syndromes. Led by Heather Hampel, MS, LGC, of the OSUCCC – James, the OCCPI network includes 50 hospitals.

The OCCPI was supported by Pelotonia, an annual grassroots bicycle tour that raises millions of dollars for cancer research at Ohio State (see story, back inside cover).

If a colorectal cancer patient is found to have an inherited cancer syndrome, his or her relatives also can be screened for it and can take heightened surveillance or preventive measures if they too are found to have the syndrome.

“The prevalence of hereditary cancer syndromes – including Lynch syndrome – among early-onset colorectal cancer patients was quite high, which presents a tremendous opportunity for us to save lives through early detection based on genomic risk factors,” says Hampel, principal investigator for the study and senior author of the JAMA Oncology paper. “It is critical that people find out at a young age if they are genetically predisposed to cancer so they can take steps to prevent cancer from occurring at all.” Read More

Ohio State Co-Leads National Precision Medicine Trial to Treat AML

The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) will play a leadership role in a groundbreaking, collaborative clinical trial for acute myeloid leukemia (AML) sponsored by the Leukemia & Lymphoma Society. Known as “Beat AML,” the trial represents unprecedented collaboration among top leukemia researchers and medical centers, non-profit organizations, pharmaceutical companies and a leading genomics information company to advance treatment for AML, a deadly disease that affects 20,000 Americans annually. John C. Byrd, MD, a Distinguished University Professor at Ohio State who also holds the D. Warren Brown Designated Chair in Leukemia Research and directs the Division of Hematology, is co-principal investigator and chief medical officer for the “Beat AML” trial. The local arm of the trial will be led by Alice Mims, MD, and William Blum, MD, both of the Division of Hematology at Ohio State. Read more and watch a video

Statewide Lung Cancer Clinical Research Initiative to Be Launched

The OSUCCC – James is set to launch a statewide clinical research initiative that takes 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, and Mary Ellen Wewers, RN, PhD, MPH, the initiative is called Beating Lung Cancer - in Ohio (BLC-IO) and will be supported by a $3 million grant from Pelotonia, an annual grassroots bicycle tour that raises money for cancer research at Ohio State. The initiative will draw upon an existing network of more than 50 partner hospitals from communities across Ohio that was established as part of the Ohio Colorectal Cancer Prevention Initiative (OCCPI), a previous statewide research initiative funded by Pelotonia. Recruitment for the new lung cancer initiative will take place over three years starting in March 2017. Read More

Brain Cancer: 2 Amino Acids May Hold Key to Better Outcomes

A study led by researchers at the OSUCCC – James indicates that the altered metabolism of two essential amino acids helps drive the development of glioblastoma (GBM), the most common and lethal form of brain cancer. The study, published in the journal Clinical Cancer Research, suggests new ways to treat the malignancy, slow its progression and reveal its extent more precisely. Specifically, the study shows that in GBM the essential amino acids methionine and tryptophan are abnormally metabolized due to the loss of key enzymes in GBM cells. The altered methionine metabolism helps activate oncogenes, while the changes in tryptophan metabolism shield GBM cells from detection by immune cells. Together, the changes promote tumor progress and cancer-cell survival. First author Kamalakannan Palanichamy, PhD, says the findings suggest that restricting dietary intake of methionine and tryptophan might help slow tumor progression and improve treatment outcomes. Read More

Biologic Age – Versus Chronologic Age – Should Drive Cancer Treatment Choices

As the baby boomer generation ages, the number of older adults with blood-based cancers is growing. For many of those patients, the best chance for a “cure” involves intensive treatments traditionally thought to be too harsh for people over age 65. Experts at the OSUCCC – James, however, say it is a patient’s overall “fitness” and biologic age—how the body has aged over time—that should guide treatment choices, not the age in calendar years. Research published by Ashley Rosko, MD, Christin Burd, PhD, and others is debunking the idea that age alone should be a limiting factor to treatment. Their team is studying the process of aging and how it impacts ability to tolerate cancer treatments. Read More

Study Suggests Radiation Plus Chemotherapy is Best Treatment for Low-Grade Brain Tumors

Recent clinical trial findings show that patients with a low-grade form of brain cancer who are treated with radiation plus a combination of chemotherapy drugs have better survival than patients treated with radiation alone. The study, published in the New England Journal of Medicine, came from a randomized phase III clinical trial of 251 people with grade 2 gliomas, tumors that occur mostly in young adults and cause progressive neurological problems and premature death. Researchers at the OSUCCC – James helped lead the study. Arnab Chakravarti, MD, professor and chair of the Department of Radiation Oncology at Ohio State and director of the brain tumor program at the OSUCCC – James, is the trial’s translational research national study chair. Read More

Nivolumab Improved Survival for Patients With Head and Neck Squamous Cell Carcinoma

Treatment with the immunotherapeutic nivolumab (Opdivo®) improved survival for patients with recurrent or metastatic head and neck squamous cell carcinoma that progressed after platinumbased chemotherapy compared with single-agent chemotherapy of the investigator’s choice, according to results from the CheckMate-141 phase III clinical trial presented at the American Association for Cancer Research (AACR) annual meeting in April 2016. Maura Gillison, MD, PhD, professor in the Department of Internal Medicine at Ohio State and member of the Cancer Control Program at the OSUCCC – James, says this study is the first randomized clinical trial to clearly demonstrate improved overall survival for patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma, adding that investigators hope the results will establish nivolumab as a new standard-ofcare option for this patient population. Read More

Primary Tumor Location Predicts Survival in Metastatic Colon Cancer, Impacts Choice of Targeted Therapy

An analysis of phase III data from a large multicenter clinical trial (CALGB/SWOG 80405) finds that primary tumor location (left versus right side) can help predict survival and guide optimal treatment choices for patients with metastatic colon cancer. The study was presented at the 2016 American Society of Clinical Oncology Annual Meeting in Chicago. Researchers analyzed 1 ,100 patients treated at hundreds of hospitals across the United States and Canada, including 30 patients treated at The OSUCCC – James. Data showed that patients with primary colon tumors originating on the left side (descending colon, sigmoid colon and rectum) survived on average significantly longer than patients whose tumors originated on the right side (the cecum and ascending colon). Patients with left-sided tumors also had a longer median overall survival (33.3 months) than patients with right-side tumors (19.4 months). Read More

Scientists Study Cancer in Dogs to Help Humans With Same Disease

A new collaborative research program pairs oncologists who treat childhood and adult sarcomas with veterinarians who manage the same cancers in canine patients. The goal, says director Cheryl London, DVM, PhD, is to accelerate the pace of translational research discoveries and new treatments for sarcoma, a diverse group of cancerous tumors that occur in soft tissue or bone. Established in 2016 by The Ohio State University College of Veterinary Medicine, the Comparative Oncology Signature Research Program is a partnership between the vet school and the OSUCCC – James that integrates nearly 40 scientists from the Ohio State colleges of Medicine, Pharmacy, Nursing and Veterinary Medicine, along with researchers from Nationwide Children’s Hospital. The program addresses a significant challenge in the current clinical trials model: the lack of a close comparative testing model for translating drug discoveries to application in human cancer. Read More

Pelotonia ‘Idea Grant’ Fuels New AML Research

Improving treatment options for one type of cancer is a launching point, not the finish line, for researchers at the OSUCCC – James. John C. Byrd, MD, director of the Division of Hematology, and his team developed a drug called ibrutinib for treating chronic lymphocytic leukemia (CLL). This daily pill sends CLL into remission and keeps it there in most cases, allowing patients to live with it, Byrd says. But this wasn’t enough. Rosa Lapalombella, PhD, of the Division of Hematology, says Byrd challenged colleagues to “move our knowledge of molecular therapeutics and molecular biology to another cancer.” Lapalombella accepted the challenge, and with funding from a Pelotonia Idea Grant she has targeted acute myeloid leukemia (AML). Aiming at cells in AML, she and her team are developing a new treatment for this complex form of blood cancer. 

Insights on Lung Microenvironment Explain Why Cancer Spreads to Lungs

The same mechanisms that prevent people from having an inflammatory response to harmless environmental exposures in day-to-day life could also allow rogue cancer cells to spread to the lungs, according to research from the OSUCCC – James. Researchers have discovered and described how the lungs’ underlying immune environment enables cancer to spread to the lungs. They reported their findings online ahead of print in the journal Cell. David Clever, PhD, first author of the manuscript, is a medical student at Ohio State who completed this research under the mentorship of Nicholas Restifo, MD, of the National Cancer Institute during the doctoral portion of Clever’s work in the Medical Scientist Training Program in The Ohio State University College of Medicine.

Survey: Majority Under 35 Think E-Cigs Are Safer; Studies Aim to Find Out

Most Americans under age 35 think that using electronic cigarettes does not cause as much damage to lung health as compared with traditional cigarettes, according to results from a new national consumer survey. In the survey, which included more than 2,000 people under 35, 44 percent of respondents reported believing that e-cigarettes are less harmful to the lungs than traditional cigarettes. Among men, that number jumped to 54 percent who think e-cigarettes are safer. The OSUCCC – James is recruiting healthy volunteers who use tobacco products for two clinical studies under way to evaluate the health effects of electronic cigarettes (known as “e-cigs” or “vaping”) and other tobacco products. “There is so much we don’t know about these new products,” says Peter Shields, MD, a thoracic oncologist and deputy director of the OSUCCC. “We have no idea where in the spectrum these are, in terms of safety…We need to figure this out.” Read More

Blocking PRMT5 Might Force Resistant Brain Tumor Cells Into Senescence

A study by OSUCCC – James researchers suggests that blocking an enzyme called PRMT5 in tumor cells could be a promising strategy for treating glioblastoma (GB), the most aggressive and lethal form of brain cancer. The study, published in the journal Oncogene, shows that knocking down PRMT5 (protein arginine methyltransferase 5) might force the cells into senescence and slow or stop tumor growth. “Our findings show that inhibiting PRMT5 can affect both mature and immature tumor cells in glioblastoma, and they underscore the importance of developing PRMT5 inhibitors as a promising therapeutic approach for patients with these tumors,” says principal investigator and OSUCCC – James researcher Balveen Kaur, PhD, professor and vice chair of research in the Department of Neurological Surgery at Ohio State. Read More

Increased Eye Cancer Risk Linked to Pigmentation Genes

New research links specific inherited genetic alterations to an increased risk for eye (uveal) melanoma, a rare form of cancer arising from pigment cells that determine eye color. In this study—co-authored by ophthalmologic pathologist and cancer geneticist Mohamed AbdelRahman, MD, PhD, of the Molecular Biology and Cancer Genetics Program at the OSUCCC – James, and by cancer geneticist Tomas Kirchhoff, PhD, of the Perlmutter Cancer Center of New York University School of Medicine—scientists reported the first evidence of a strong association between genes linked to eye color and development of uveal melanoma. The research team reported its findings in the medical journal Scientific Reports. Read More

NCH Researchers Describe New Type of Cancer Therapy

A study conducted at Nationwide Children’s Hospital (NCH) has found that a new chemotherapy is effective against both pediatric and adult cancers, and that it allows other chemotherapies to more readily reach their targets. Published in the journal Pharmaceutical Research, the study describes a novel class of antitumor amphiphilic amines (RCn) based on a tricyclic amine hydrophilic head and hydrophobic linear alkyl tail of variable length. Senior author on the paper is Timothy Cripe, MD, PhD, principal investigator in the Center for Childhood Cancer and Blood Disease in The Research Institute at NCH. Cripe, a professor in The Ohio State University College of Medicine, Department of Pediatrics, also is a member of the Translational Therapeutics Program at the OSUCCC – James. Read More

New Drug Shows Promise in Treating Head and Neck Cancer Caused by HPV

A new drug shows great promise in melting away the cancer cells in head and neck tumors caused by human papillomavirus (HPV). The drug, which reactivates the anticancer p53 gene, was developed under the leadership of Quintin Pan, PhD, a professor in the Department of Otolaryngology – Head and Neck Surgery at Ohio State and a member of the Translational Therapeutics Program at the OSUCCC – James. Pan’s drug, OHM1, will soon begin clinical trials and could revolutionize the treatment of head and neck caused by HPV. The drug could also be used to treat cervical and anal cancers, says Ted Teknos, MD, who chairs the Otolaryngology Department and is Pan’s mentor. Read More

Study Identifies Possible Marker for Lung Cancer Chemotherapy

The activity level of a certain gene in lung tumors might identify patients who likely will be helped by a particular chemotherapy regimen given to prevent recurrence after surgery, according to a study led by OSUCCC – James researchers and published in the journal Clinical Cancer Research. The study examined the expression of a gene called SMARCA4/BRG1 in tumor cells from patients with earlier-stage non-small-cell lung cancer (NSCLC). The researchers found that low SMARCA4 expression signals a poor prognosis, but also a significant sensitivity to the chemotherapy drug cisplatin. First author Erica Bell, PhD, says SMARCA4, which is commonly mutated in NSCLC, might identify patients who will benefit from cisplatin and other platinum-based drugs. Read More

Argentine Tango Therapy Helps Restore Balance for Cancer Patients With Neuropathy

Dance as a form of therapy—specifically Argentine tango—has the potential to significantly improve balance and reduce the risk of falls among cancer patients experiencing peripheral neuropathy, according to research conducted by a multidisciplinary team at Ohio State. The pilot study was funded by Pelotonia, an annual grassroots bicycle tour that raises money for cancer research at Ohio State. Pelotonia fellow and pre-med/dance major Mimi Lamantia collaborated with Lise Worthen-Chaudhari, a physical rehabilitation specialist who studies movement at The Ohio State University Wexner Medical Center Neurological Institute, to conduct the research study. Read More

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