The OSUCCC - James offers this compilation of research and grant news from 2022. Study reveals male sex hormones are new targets for cancer immunotherapy Patients with cancers stemming from non-reproductive organs, such as bladder and liver cancer, have striking discrepancies in incidence, progression, response to treatment and survival outcomes depending on their sex. In almost all cases, male patients have worse prognoses and outcomes, a phenomenon that has puzzled the scientific community for decades. A study published in the journal Science Immunology and led by researchers at the Pelotonia Institute for Immuno-Oncology (PIIO) at the OSUCCC – James examined the differences in intratumoral immune responses between male and female cancers of non-reproductive origin. PIIO Founding Director Zihai Li, MD, PhD, was senior corresponding author for the study, which reported a landmark finding that describes how male sex hormones called androgens contribute to cancer-related sex bias via the modulation of CD8+ T cells.    Discovery could ‘revolutionize’ understanding of aggressive cancer growth and spread New data show that ammonia, typically known as a waste byproduct from protein degradation that is excreted from the human body through urine, plays a key role in fueling the rapid growth of certain aggressive forms of cancer. Representing the culmination of more than a decade of laboratory research, an OSUCCC – James team reported findings that ammonia is not a waste molecule but plays a critical role in activating fat production in cancer cells, promoting cancer growth and spread. Their findings appeared in the journal Nature Metabolism. Deliang Guo, PhD, professor in the Department of Radiation Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, was senior author; Chunming Cheng, PhD, a research scientist in Radiation Oncology, was first author.   Chronic lower extremity lymphedema has dramatic impact on physical function in large number of older female cancer survivors A study led by the OSUCCC – James found that nearly one third of older adult female survivors of colorectal, endometrial and ovarian cancer have quality of life-impacting challenges with physical activity due to chronic swelling (lymphedema) in the lower extremities. This was the first study to assess lower lymphedema in colon cancer survivors. The researchers say these findings call attention to the importance of regularly assessing lower-extremity lymphedema in older survivors of cancer – something that’s not part of current national clinical practice guidelines – so that effective and timely interventions can be given to preserve physical ability and independence. They reported their findings in the journal JAMA Network Open. Electra Paskett, PhD, associate director of population sciences and community outreach at the OSUCCC – James, was senior author.   Study identifies new molecular target for cancer therapy   Researchers at the OSUCCC – James identified a molecular drug target that could result in new cancer drugs with fewer side effects. Previous studies had shown that vascular endothelial growth factor-A (VEGF-A) – a potent cytokine (signaling protein) – and dopamine (a neurotransmitter/neurohormone) play essential roles in many physiological and pathological functions. In this study, Sujit Basu, MD, PhD, a member of the Translational Therapeutics Program at the OSUCCC – James, and colleagues conducted further preclinical analysis of VEGF-A as a target for the development of cancer therapy approaches. They found for the first time that VEGF-A can increase expression of dopamine D2 receptors on endothelial cells that can then be stimulated to stop the growth of blood vessels that fuel the growth and spread of several diseases, including colon cancer, endometriosis and ovarian hyperstimulation syndrome. The study was published in the Journal of Cell Science.   New initiative aims to improve diagnosis and treatment of children with solid tumors through molecular analysis The National Cancer Institute (NCI), Children’s Oncology Group (COG) and Nationwide Children's Hospital (NCH) in Columbus, Ohio, are poised to change the direction of pediatric cancer diagnosis and care through the Molecular Characterization Initiative (MCI), a project that will collect, analyze and report clinical molecular data to support COG-affiliated clinicians in choosing the best treatment for each child. This program is part of the NCI Childhood Cancer Data Initiative (CCDI). Children, adolescents and young adults newly diagnosed with a central nervous system tumor, soft tissue sarcoma or rare tumor, and who are receiving care at a hospital affiliated with the COG, are eligible to participate in the initiative, the largest of its kind in the United States. Principal investigator for the MCI contract is Elaine Mardis, PhD, co-executive director of the Institute for Genomic Medicine at NCH and co-leader of the Translational Therapeutics Program at the OSUCCC – James.   OSUCCC – James leads endometrial cancer project associated with Moonshot Initiative With funding from the NCI Molecular Profiling to Predict Response to Treatment (MP2PRT) Program, experts led by the OSUCCC – James are providing new data on the molecular features that characterize clinically aggressive endometrial cancers. The project – associated with the national Cancer Moonshot℠ Initiative established in 2016 to accelerate cancer research – will build upon earlier endometrial cancer studies by The Cancer Genome Atlas, which have shown that there is promise for improved prognostication and personalization of treatment with further molecular classification. Principal investigator is Casey Cosgrove, MD, assistant professor in the Division of Gynecologic Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James. Project co-investigator is Ashley Felix, PhD, associate professor in the College of Public Health, Division of Epidemiology, at Ohio State and member of the Cancer Control Program at the OSUCCC – James.   Lung cancer patients coped with pandemic better than many peers Far from being hobbled by fears of COVID-19, lung cancer patients showed less depression and anxiety during the pandemic than their healthy peers, according to findings from an OSUCCC – James study published online in the Journal of the National Comprehensive Cancer Network. Barbara Andersen, PhD, Distinguished University Professor in the Department of Psychology at Ohio State and member of the Cancer Control Program in the OSUCCC – James, was co-author of the study, which included other OSUCCC – James researchers as well as Ohio State psychology students. Data came from 76 patients with advanced-stage non-small cell lung cancer who were participants in Beating Lung Cancer in Ohio (BLCIO), an OSUCCC – James statewide initiative partially funded by Pelotonia.   Study shows menthol cigarette alternatives pose significant addiction and health risks  In April 2022, the U.S. Food and Drug Administration (FDA) issued proposed product standards banning menthol flavoring in cigarettes and cigars; however, the benefits of these standards could be weakened by the role of substitute products still available in the market. Tobacco researchers at Ohio State and Rutgers University urge the FDA to maximize the benefits of menthol cigarette ban restrictions by extending the ban to include potential substitutes, particularly menthol pipe tobacco and cigarette tubes, based on new evidence showing the appeal and addiction potential of these substitutes in adults who smoke menthol cigarettes. Theodore Wagener, PhD, director of the Center for Tobacco Research at Ohio State, was corresponding author of the study, which was published in the journal Tobacco Control.    Ohio State researchers lead international trial to compare open vs. minimally invasive surgery for treating early-stage cervical cancer  Researchers at the OSUCCC – James are leading an international clinical trial to determine whether minimally invasive surgery, called robotic-assisted laparoscopy (small-incision surgery), is better or worse than open surgery (laparotomy) when performing a radical hysterectomy to treat cervical cancer. Sponsored by the Gynecologic Oncology Group (GOG), the trial is led by Study Chair Kristin Bixel, MD, assistant professor in the Division of Gynecologic Oncology at Ohio State. Allison Quick, MD, associate professor in the Department of Radiation Oncology at Ohio State, is one of four co-chairs.   Young Black patients with AML have worse outcomes than white patients of same age  Young adult Black patients with acute myeloid leukemia (AML) are five times more likely than comparable white patients to die within 30 days of beginning treatment and twice as likely to die within five years, despite receiving similar state-of-the-art treatment, according to research at the OSUCCC – James. “To our knowledge, this is the first study to examine how molecular genetic alterations contribute to outcomes in young Black people with AML compared with their white counterparts,” said lead author Karilyn Larkin, MD, assistant professor in the Division of Hematology at Ohio State and member of the Leukemia Research Program at the OSUCCC – James. “We found that, among young Black and white patients who received similar intensive therapy on clinical trials, outcomes were dramatically inferior for Black patients compared with white patients. This disparity occurred predominantly among patients aged 18 to 29 years.” The study appeared in the journal Blood Advances.    Scientists report single-dose cancer immunotherapy via gene transfer Researchers at Nationwide Children’s Hospital and the OSUCCC – James reported proof-of-principle results for a new gene therapy cancer treatment. The off-the-shelf, single-dose immunotherapy serves as an alternative to chimeric antigen receptor (CAR) T-cell therapy and can be engineered to be on-demand. T-cells redirected to cancer cells either via a CAR-T or a bispecific molecule have been game-changers in treating certain leukemias and lymphomas. Even so, there are challenges associated with these treatments; for instance, CAR-T cells are expensive and cumbersome to manufacture, while bispecifics require long infusions. Timothy Cripe, MD, PhD, chief of the Division of Hematology and Oncology at Nationwide Children’s and member of the Translational Therapeutics Program at the OSUCCC – James, was lead author of the study, which was published in the journal Science Advances.    Investigators develop technique to edit NK cells to target cancer cells  The third of three major challenges in enabling the clinical potential of natural killer (NK) cells for cancer therapy has been addressed, thanks to the combined talents of gene editing experts and NK cell specialists at Nationwide Children’s Hospital and the OSUCCC – James. The research, published in the journal Cell Reports Methods, was led by Dean Lee, MD, PhD, director of the Cellular Therapy and Cancer Immunology Program at Nationwide Children's and member of the Leukemia Research Program at the OSUCCC – James, and Meisam Naeimi Kararoudi, MD, PhD, director of the CRISPR/Gene Editing Core and a principal investigator in the Center for Childhood Cancer and Blood Diseases at Nationwide Children’s. The scientists found that coupling adeno-associated viral (AAV) vectors with a gene-editing technology called CRISPR enables effective NK cell editing for subsequent enhanced efficacy against acute myelogenous leukemia (AML) cells.   Flu vaccine may become new melanoma treatment  The flu vaccine could double as a breakthrough treatment for advanced melanoma, according to Ohio State research. Skin cancer specialists at the OSUCCC – James are conducting an immunotherapy study that may lead to a new use for influenza vaccination through a more targeted method of injection. Carlo Contreras, MD, associate professor in the Division of Surgical Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, explains that, instead of administering the annual flu vaccine in a patient’s arm, clinicians would inject it directly into the melanoma so it can recognize and kill cancer cells.   Study suggests a way to re-energize tired T-cells when treating cancer viral infections A new study by researchers at the OSUCCC – James suggests a way to re-energize critical killer immune cells that have become exhausted when fighting cancer or chronic viral infections. Immune cells called CD8 T-cells are important in the immune system’s efforts to eliminate cancer cells and viral infected cells from the body. These cells are also key players in immune therapies called immune checkpoint blockade and CAR T-cell therapy. For this animal and cell study, researchers first developed a new model system to study human CD8 T-cell dysfunction and whether the dysfunction can be reversed. They report their findings in the journal Nature Immunology. Hazem Ghoneim, PhD, assistant professor in the Department of Microbial Infection and Immunity at Ohio State and member of the Cancer Biology Program at the OSUCCC – James, was principal investigator.   Immuno-oncology treatment pre-surgery is safe, effective option for localized non-small cell lung cancer  The immuno-oncology drug atezolizumab is a safe and effective treatment for stage IB-IIIB non-small cell lung cancer patients prior to lung cancer surgery, according to data from a study led by researchers at the OSUCCC – James as part of the national Lung Cancer Mutation Consortium 3 study. Researchers found that the survival of patients in this new study was far better – about 80% at three years post treatment and approximately twice as good as that which would be expected with surgery and chemotherapy alone. Study findings appeared in the journal Nature Medicine. The study was led by David Carbone, MD, PhD, director of the Thoracic Oncology Center and co-leader of the Translational Therapeutics Program at the OSUCCC – James.   Survey: most women unaware of the signs of an aggressive form of breast cancer  A national survey commissioned by the OSUCCC – James found that most women don’t know the unusual symptoms of an aggressive and deadly form of the disease known as inflammatory breast cancer (IBC). The survey, conducted online among 1,100 U.S. women of ages 18 and older, revealed that while four of five women (78%) recognize a lump as a sign of breast cancer, less than half would flag redness of the breast (44%), pitting or thickening of the skin (44%), or one breast feeling warmer or heavier than the other (34%) as possible symptoms of breast cancer, specifically IBC. The OSUCCC – James has created a multidisciplinary IBC Program at the Stefanie Spielman Comprehensive Breast Center that includes surgical, medical and radiation oncologists, as well as breast radiologists, plastic/reconstructive surgeons, physical therapists and nurses.    Study sheds light on understudied breast cancer type A multi-center analysis of patients with invasive lobular carcinoma, or ILC, the second most common histological subtype of invasive breast cancer in the United States, showed that, despite its prevalence, ILC is detected later and has worse outcomes than the predominant subtype of invasive breast cancer, known as invasive ductal carcinoma (IDC), or no special type. Published in the Journal of the National Cancer Institute, the study of more than 33,000 patient records from three cancer centers (the OSUCCC – James, UPMC Hillman Cancer Center, and Cleveland Clinic Cancer Center) shows that ILC and IDC are biologically distinct, highlighting important differences between the two diseases and a need for specific detection and treatment options for the lobular subtype. Nicole Williams, MD, associate professor in the Division of Medical Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, was a co-author of the study.    New approach to managing post-surgery pain reduces opioid-based medication use by 50% Effective pain management is critical to surgical recovery, but in the past decade this has often relied heavily on opioid-based medications that can cause side effects that slow physical recovery and put patients at risk for pain medication dependency and addiction. The OSUCCC – James has implemented a radically different approach to post-surgery pain management that is focused on maximizing non-opioid techniques first, using opioids only as a back-up option. Leading this initiative is Michelle Humeidan, MD, PhD, clinical associate professor in the Department of Anesthesiology at Ohio State, who says data show that non-opioid pain-management options can result in less pain, less nausea, shorter hospital stays and reduced costs.   To rev up CAR T-cell therapy, inhibit the SUSD2 membrane protein, study suggests Inhibiting a particular protein in cancer-killing immune cells might improve the long-term effectiveness of CAR T-cell and other immune checkpoint therapies, according to a new study by researchers at the OSUCCC – James. Published in the journal Nature Immunology, the animal study examined the function of a membrane protein called SUSD2. The molecule is expressed by cancer-killing immune cells called CD8 T cells, but its role in antitumor immunity remains unknown. It is also expressed in several human cancers, including breast, ovarian, non-small cell lung, gastric and colorectal cancer. Principal investigator was Haitao Wen, PhD, MD, associate professor in the Department of Microbial Infection and Immunity at Ohio State, and member of the Molecular Carcinogenesis and Chemoprevention Program at the OSUCCC – James.   OSUCCC – James large grant highlights: Ohio State receives funding to study novel biodosimetry solutions for evaluation of radiation exposure   OSUCCC – James researchers entered a $9.42 million federal cooperative agreement that will help them further develop Ohio State’s biodosimetry technology to discover noninvasive biomarkers for radiation exposure. Awarded by the Intelligence Advanced Research Projects Activity (IARPA), an organization within the Office of the Director of National Intelligence, and the Army Research Office (ARO), the agreement aligns with the IARPA’s mission “to push the boundaries of science to develop solutions that empower the intelligence community to do its work better and more efficiently for national security.” Principal investigator (PI) Naduparambil Jacob, PhD, associate professor in the Department of Radiation Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, says this work is important because of the possible major health consequences of radiation exposure, including cancer. Being able to determine the amount and range of exposure would help clinicians more quickly and accurately mitigate short- and long-term effects.   NCI grant will support study of factors leading to CLL  Researchers at the OSUCCC – James and the Mayo Clinic will use a five-year, $4.35 million grant from the NCI to study genetic and epigenetic factors that cause a precursor state of chronic lymphocytic leukemia (CLL) to progress to the onset of this generally incurable malignancy. Christopher Oakes, PhD, of the Leukemia Research Program at the OSUCCC – James, is a PI for this grant along with Susan Slager, PhD, of the Mayo Clinic in Rochester, Minnesota, and Esteban Braggio, PhD, of the Mayo Clinic in Phoenix/Scottsdale, Arizona. Oakes also is an associate professor in the Division of Hematology and in the Department of Biomedical Informatics at Ohio State. In their project abstract, the researchers state that, because CLL impairs the body’s immune response, patients with this disease may have a high number of morbidity and mortality complications, including increased risk of infections and secondary cancers. “Identifying individuals who are at markedly higher risk of developing this disease may enable future prevention strategies,” they wrte.   Researchers awarded NCI grant to help boost clinical trial accrual of underrepresented populations Researchers at the OSUCCC – James received a five-year, $3.5 million grant from the National Cancer Institute (NCI) to support Ohio State’s “Connecting Underrepresented Populations to Clinical Trials (CUSP2CT)” project, which is designed to increase referral and accrual of racial/ethnic minorities to cancer prevention, control and treatment trials at the OSUCCC – James. PIs for the grant are Electra Paskett, PhD, and Cheryl Lee, MD. Paskett is professor and director of the Division of Cancer Prevention and Control at Ohio State. At the OSUCCC – James, she is associate director for population science, co-leader of the Cancer Control Program and director of the Center for Cancer Health Equity. Lee is professor and chair of the Department of Urology at Ohio State and a member of the Translational Therapeutics Program at the OSUCCC – James.   NCI grant will fund study of treatment patterns in subset of patients with AML OSUCCC – James researchers will use a five-year, $3.32 million grant from the NCI to help understand treatment response patterns and therapy resistance in a subset of patients with acute myeloid leukemia (AML) whose disease is characterized by isocitrate dehydrogenase 1 (IDH1) and IDH2 enzyme mutations. PIs are Ann-Kathrin Eisfeld, MD, Alice Mims, MD, and Elaine Mardis, PhD. Eisfeld and Mims serve respectively as assistant and associate professor in the Division of Hematology at Ohio State and are in the Leukemia Research Program at the OSUCCC – James. Mardis is a professor in the Department of Pediatrics at Ohio State and co-leader of the Translational Therapeutics Program at the OSUCCC – James. Mims also is clinical section head for the Acute Leukemia Program in the Division of Hematology and Eisfeld is director of the Clara D. Bloomfield Center for Leukemia Outcomes Research.   Researcher obtains federal grant to study impact of retail marijuana excise tax structures on marijuana consumption Ce Shang, PhD, assistant professor in the Division of Medical Oncology at Ohio State and member of the Cancer Control Program at the OSUCCC – James, received a five-year, $3.3 million grant from the National Institute on Drug Abuse to evaluate how excise tax structures impact marijuana consumption and product choices among different marijuana forms and between legal and illegal products. The empirical evidence will inform how to set excise tax structures to mitigate harms for states contemplating taxation policies as they legalize, and for states and localities with legal retail sales contemplating reforms to their current tax structures. Shang is a health economist with extensive experience in regulatory science.   Scientists land NCI grant to develop therapy against rare large B-cell lymphoma The NCI awarded a five-year, $2.9 million grant to help researchers at the OSUCCC – James study a rare form of large B-cell lymphoma (LBCL) and develop a targeted therapy for patients with this currently incurable cancer. PI is Lapo Alinari, MD, PhD, assistant professor in the Division of Hematology at Ohio State and member of the Leukemia Research Program at the OSUCCC – James. In their project abstract, Alinari and colleagues state that patients with LBCL that overexpresses the c-Myc protein have a significantly worse prognosis than patients with the cMyc-negative form of the disease – highlighting the need for novel therapeutic strategies.   Federal grants will boost efforts for earlier detection of endometrial and ovarian cancer The U.S. Department of Defense (DOD) awarded a pair of grants totaling approximately $2.65 million to help OSUCCC – James researchers identify cellular biomarkers that could lead to earlier detection of endometrial (uterine) and ovarian cancer. A four-year, $1.94 million grant from the DOD Peer-Reviewed Cancer Research program will address gaps in early detection and diagnosis of endometrial cancer. A three-year, $710,000 grant from the DOD Ovarian Cancer Research Program will enhance efforts for earlier detection of high grade serous ovarian cancer (HGSOC). PI for both is Selvendiran Karuppaiyah, PhD, associate professor in the Department of Obstetrics and Gynecology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James.   NCI grant will aid study of racial disparities in endometrial cancer treatment  The NCI awarded a five-year, $2.42 million grant to help a team led by an OSUCCC – James researcher to determine why Black women receive lower levels of endometrial cancer (EC) treatment that is concordant with National Comprehensive Cancer Network (NCCN) guidelines. PI for the study is Ashley Felix, PhD, associate professor in the College of Public Health, Division of Epidemiology at Ohio State, and a member of the Cancer Control Program at the OSUCCC – James. Felix and colleagues state in their project summary that EC exhibits one of the worst racial disparities for solid tumors, noting that the mortality gap between Black and white women with EC has increased from 79.5% in 1992-2001 to 97.8% in 2014-2018.   NIH grant to help scientists study cancer treatment links to heart disease A five-year, $2 million grant from the National Heart, Lung and Blood Institute at the National Institutes of Health (NIH) is helping researchers at Ohio State probe a relatively new area of medical science that works to link certain cancer treatments to heart failure. The scientists state the 14 million cancer survivors in the United States “demonstrate continued improvements in anticancer treatment efficacy; yet, this success has been tempered by a parallel rise in the incidence of cancer treatment-related cardiotoxicity, leading to morbidity and mortality.” PI is Sakima Smith, MD, associate professor in the Division of Cardiovascular Medicine, and holder of the Bob Frick Research Chair in Heart Failure and Arrhythmia. Smith and colleagues are associated with the Bob and Corrine Frick Center for Heart Failure and Arrhythmia at Ohio State.   NCI grant to help scientists study protein that promotes AML OSUCCC – James researchers who have discovered that a protein called EGFL7 promotes acute myeloid leukemia (AML) will use a five-year, $1.5 million grant from the NCI to study how the protein facilitates AML and develop combination therapies to combat it. PI is Adrienne Dorrance, PhD, assistant professor in the Division of Hematology at Ohio State and member of the Leukemia Research Program at the OSUCCC – James. In their project abstract, the researchers state that AML is a heterogeneous malignancy of the blood and bone marrow and note that, along with genetic mutations in the leukemic cells themselves, alterations in the bone marrow microenvironment also play an important role in leukemia transformation, therapy resistance and relapse.   NCI grant supports study of multiple myeloma growth and immune system evasion Researchers at the OSUCCC – James received a five-year, $1.26 million grant from the NCI to learn how a protein called CD56 supports multiple myeloma (MM) growth and evades the body’s immune system. Principal investigator for the grant is Francesca Cottini, MD, assistant professor in the Division of Hematology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James. In her project abstract, Cottini states that MM is a currently incurable blood cancer for which there are no targeted therapies despite major differences among patients in terms of genetic abnormalities, gene expression profiles or immune signatures.