Researchers from Vanderbilt-Ingram Cancer Center will present findings from clinical trials, laboratory discoveries and innovations in caring for patients with hematologic cancers and other blood diseases at ASH 2025 in Orlando, Florida, Dec. 6-9. 

ASH 2025 is the American Society of Hematology Annual Meeting and Exposition. Established in 1958, ASH is the world’s largest professional organization for clinicians and scientists who study blood diseases.  

Three of the presentations from Vanderbilt-Ingram researchers will focus on chimeric antigen receptor T-cell (CAR-T) therapies, a form of immunotherapy that involves treating cancer with white blood cells that have been reengineered to attack cancer cells. Vanderbilt-Ingram is an international leader in advancing the efficacy of and expanding access to CAR-T therapies.

Olalekan Oluwole, MBBS, MPH, associate professor of Medicine, who leads the cellular therapy research program at Vanderbilt-Ingram, will present data on health care resource utilizations of the therapies in U.S. patients treated at newly authorized treatment centers. He will also provide an overview of outcomes for inpatient and outpatient CAR-T treatment. Grace Mercadante, MD, will present data on the impact of clonal hematopoiesis on CAR-T therapy. 

Michael DeBaun, MD, MPH, the J.C. Peterson, MD, Professor of Pediatrics and founder and director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, will speak at a special session focusing on ASH’s sickle cell disease initiative. He will present findings from “Sickle Cell Trait Does Not Cause ‘Sickle Cell Crisis’ Leading to Exertion Related Death: A Systematic Review.” 

Other topics researchers will address include acute myeloid leukemia, myelodysplastic syndrome, drug resistance, potential adverse reactions and risk comparisons of treatments, pediatric blood disorders, multiple myeloma, bispecific antibody treatment, and graft-versus-host disease. 

A complete list of presentations from Vanderbilt researchers follows: 

Sally Momoh, MD – Sex-related differences in silent cerebral infarction burden among adults with sickle cell disease 

Jamila Mammadova, MD – Behind the blood-brain barrier: Contemporary screening practice patterns and trends of central nervous system involvement in acute myeloid leukemia treated with intensive regimens and hypomethylating agent/venetoclax 

Alyssa Jarabek – Impact of innate immune memory on myelodysplastic syndrome progression by TET2-driven inflammation 

Raymond Zhang – VISTA contributes to disease progression in high-risk myelodysplastic syndrome 

Mattew Villaume, MD, PhD – EB2023 primes mitochondria for BCL2 dependence and induces pyroptotic cell death via AMPK signaling and the unfolding protein response 

Grace Mercadante, MD – The impact of clonal hematopoiesis on CAR-T cell therapy outcomes: a single-center analysis 

Ghadeer Dawwas, PhD, MSc, MBA – Risk of serious bleeding with concomitant use of apixaban or rivaroxaban with amiodarone compared to flecainide or sotalol in patients with atrial fibrillation  

Olalekan Oluwole, MBBS, MPH – Real-world health care utilization following CAR-T cell therapy in U.S. patients treated in newly authorized treatment centers 

Erin Christensen, MS, DO – A case series of pediatric patients with congenital thrombotic thrombocytopenia purpura treated with recombinant ADAMTS13 

Andrew Jallouk, MD, PhD – Real-world outcomes of mosunetuzumab use in indolent and aggressive lymphomas  

Bhagirathbhai Dholaria, MBBS – Characterization of a population with newly diagnosed standard risk multiple myeloma by 2025 ims/IMWG definition with exceptional long-term outcomes after fixed duration therapy 

Y. Emily Chu – The acute myeloid leukemia microenvironment is defined by ineffective immune surveillance despite the presence of activated, clonally-expanded CD8 T cells with preserved effector function 

Michael DeBaun, MD, MPH – Findings from “Sickle cell trait does not cause ‘sickle cell crisis’ leading to exertion related death: a systematic review ”

Mattew Villaume, MD, PhD – F1 subunit-specific ATP synthase inhibition disrupts AML mitochondrial metabolism distinctly from other electron transport chain inhibitors 

Lauren Klein, MD, – Early weight gain predicts nutritional recovery in children with sickle cell anemia and severe acute malnutrition in Nigeria 

Olalekan Oluwole, MBBS, MPH – U.S. cost consequence and time toxicity model for advanced therapies in the treatment for relapsed/refractory third-line or later diffuse large B-cell lymphoma: a comparison of axicabtagene ciloleucel with bispecific antibodies 

Olalekan Oluwole, MBBS, MPH – Outcomes of inpatient and outpatient CAR-T in newly authorized treatment centers in the United States 

Elizabeth Pollard, MD – Leukapheresis for acute leukemia with hyperleukocytosis: line complications, resource utilization, and early mortality outcomes 

Carrie Kitko, MD – Long-term treatment duration and safety of axatilimab among patients with chronic graft-versus-host disease in AGAVE-201 

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Researchers at Vanderbilt University Medical Center and the University of Calgary have established an analytical framework that integrates genomic, proteomic and electronic health record data to identify cancer risk proteins and therapeutics for cancer prevention.

Their study, reported Dec. 2 in the American Journal of Human Genetics, identifies previously unreported protein biomarkers and candidate drug targets across six major cancer types and highlights approved drugs with potential cancer preventive effects.

To date, genome-wide association studies (GWAS) have identified several hundred genetic variants associated with increased risk for breast, colorectal and prostate cancer, and several dozen risk variants for other cancers, including lung, pancreatic and ovarian cancer.

“Previous research, including our work, has identified hundreds of putative cancer susceptibility genes that could be regulated by these risk variants; however, most dysregulated gene expression has not been thoroughly investigated at the protein level,” said Xingyi Guo, PhD, associated professor of Medicine in the Division of Epidemiology at VUMC.

Guo is a co-senior author of the current study with Zhijun Yin, PhD, MS, associate professor of Biomedical Informatics at VUMC, and Quan Long, PhD, associate professor of Biochemistry and Molecular Biology at the University of Calgary.

“To deepen the understanding of causal mechanisms and enhance drug discovery efforts, it is imperative to explore data from transcriptomic to proteomic studies,” Yin said.

In the current study, the investigators integrated large GWAS data for breast, colorectal, lung, ovarian, pancreatic and prostate cancers and population-scale proteomics data from over 75,000 participants (combined from the Atherosclerosis Risk in Communities study, deCODE genetics, and UK Biobank Pharma Proteomics Project) to identify risk proteins associated with each cancer.

They identified 365 proteins associated with cancer risk, and through further analysis narrowed the list to 101 proteins, including 74 not reported in previous studies. Using a variety of pharmaceutical databases, the researchers comprehensively annotated the risk proteins as therapeutic targets of approved drugs or drugs in clinical testing. The idea, they said, is to find drugs that can potentially be repurposed for cancer prevention.

“Traditional drug discovery faces challenges of escalating costs, lengthy timelines, and high failure rates. Drug repurposing is a promising strategy to identify new applications for existing drugs with well-documented characteristics,” Guo said.

Among the 101 risk proteins, the researchers identified 36 druggable proteins potentially targeted by 404 drugs already approved or in clinical trials. Nineteen of the druggable proteins were targeted by drugs approved or in trials to treat cancer. The researchers compared drug effects using data from more than 3.5 million electronic health records (EHRs) from VUMC. They demonstrated in simulated trials with EHR data that several approved drugs, for example the diuretic medication acetazolamide, were associated with reduced colorectal cancer risk.

“Our findings offer additional insights into therapeutic drugs targeting risk proteins for cancer prevention and intervention. It is essential to evaluate the effects of the reported candidate drugs through both in vitro and in vivo assays in future research,” Yin said.

Co-first authors of the AJHG paper are Qing Li,PhD; Qingyuan Song; and Zhishan Chen, PhD. The research was supported by the National Institutes of Health (grants R37CA227130, R01CA269589, R01CA297582).

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While most women over age 50 schedule mammograms for breast cancer, only a minority who are also eligible for low-dose CT scans for lung cancer undergo those potentially lifesaving screenings. A new study shows that targeted outreach can close the gap.

The study results, published Dec. 1 in the Journal of the American College of Radiology, showed that the improvement in lung cancer screenings exceeded the target enrollment set by the researchers. The study also demonstrated that two different types of outreach initiatives were effective in increasing uptake. Called CALM, an acronym for Coordinate A Lung screening with Mammography, the study was funded by the American Cancer Society.

At one academic medical center, a research team from pulmonary medicine determined eligibility by manual review of smoking history in electronic health records and then contacted patients directly to inform them of eligibility. The team also conducted surveys at mammography locations about smoking history. They had a target enrollment of 200 new patients for lung cancer screening and exceeded it by enrolling 214 patients.

At the other academic center, researchers from radiology identified patients eligible for lung screenings one month prior to their mammography appointments through a review of electronic health records. The patients were offered the opportunity to have both cancer screenings on the same day at the same location. They also exceeded their target enrollment of 322 patients by enrolling 445 patients.

“For years, we have recognized that many women screened for breast cancer are in fact dying from lung cancer. This study allowed us the opportunity to inform women and their referring providers of lung screening eligibility and to facilitate lung screening exams.  We are incredibly grateful for the American Cancer Society and for the National Lung Cancer Roundtable as they supported this multicenter initiative.  We plan to continue these efforts at VUMC and with institutions across the country to save more lives,” said Kim Sandler, MD, professor of Radiology and Radiological Sciences at Vanderbilt University Medical Center, director of the Vanderbilt Lung Screening Program, and the study’s corresponding author and co-principal investigator.

A previous study revealed that 58% of women who were eligible for lung cancer screening had reported having a mammogram within two years compared to only 7.9% who underwent lung cancer screening. Overall, participation in lung cancer screening by both men and women is low, with less than 20% of those eligible for low-dose CT scans receiving the screenings.

“It has been more than 10 years since annual screening for lung cancer was recommended, and screening rates still are disappointingly low. There are many reasons for these low rates, but mostly identifying eligible individuals is challenging in the primary care setting, and there is evidence showing a surprising lack of awareness about lung cancer screening among eligible individuals. The CALM model demonstrates we can successfully recruit eligible women through mammography screening. Perhaps we also will be able to enlist them to encourage eligible family members to have a conversation about lung cancer screening with their health care providers. There is enormous potential here, and the ACS is thrilled with the outcome of this study,” said Robert Smith, PhD, senior vice president and director of the American Cancer Society Center for Early Cancer Detection and the study’s other co-principal investigator.

The researchers hypothesized that mammography screening could be a “teachable moment” for women who are also eligible for lung cancer screening. The study period was from November 2019 to December 2021, but data from 2020 was excluded because of the disruptions in health care screenings due to the onset of the COVID-19 pandemic. Initially, women were considered eligible for lung cancer screening from ages 55 to 80 with a 30 pack-year history of smoking; guidelines expanded in 2021, and women were eligible beginning at age 50 with a 20 pack-year history. One pack year is equal to smoking an average of 20 cigarettes, or one pack, every day for a year. A person who has smoked half a pack per day for 30 years has a 15 pack-year history.

Other VUMC authors on the study are Caroline Godfrey, MD, MPH, Valerie Welty, PhD, Stephen Deppen, PhD, MA, Alexis Paulson, MS, Shanna Joyner, Hannah Marmor, MD, MPH, Grace Wallace, CCRC, Lauren Hatcher, MD, MBA, Landon Fike, MD, and Arulita Gupta, MD.

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