A two-drug combination for treating advanced kidney cancer had sustained and durable clinical benefit in more than five years of follow-up, according to a study published Aug. 1 in Nature Medicine. 

The study reports final clinical data and biomarker analyses from the Phase 3 KEYNOTE-426 trial, which compared the drug combination pembrolizumab plus axitinib versus the single drug sunitinib for patients with previously untreated advanced clear cell renal cell carcinoma, the most common type of kidney cancer.

“KEYNOTE-426 was the first trial to combine a PD-1 inhibitor immunotherapy (pembrolizumab) with a VEGF receptor inhibitor antiangiogenic drug (axitinib) in the first-line setting for advanced renal cell carcinoma. It therefore has the longest follow-up duration among the various trials comparing these types of drug combinations,” said Brian Rini, MD, a medical oncologist at Vanderbilt-Ingram Cancer Center and the study’s lead and corresponding author. 

Immunotherapy drugs like pembrolizumab stimulate the immune system to kill tumor cells. VEGF receptor inhibitors like axitinib and sunitinib block angiogenesis — the development of blood vessels that tumors need to grow and spread. Pembrolizumab plus axitinib and other immunotherapy-antiangiogenic drug combinations are now standard first-line treatments for advanced kidney cancer. 

“Before the development of antiangiogenic drugs and immunotherapies, advanced renal cell carcinoma had a very poor prognosis. These drug combinations have dramatically improved treatment options and outcomes for patients,” said Rini, Thomas F. Frist Sr. Professor of Medicine. 

The first interim analysis of outcomes from KEYNOTE-426, published Feb. 16, 2019, in the New England Journal of Medicine, demonstrated that trial participants treated with pembrolizumab plus axitinib had longer overall and progression-free survival, and higher objective response rates compared to those taking sunitinib. The median follow-up was 12.8 months. 

Now, with a median follow-up of 67.2 months, the current analysis confirms and extends the interim analysis and provides valuable information about biomarkers that could help guide treatment decisions. 

The study in Nature Medicine reports that pembrolizumab plus axitinib had longer overall survival (47.2 months versus 40.8 months for sunitinib) and longer progression-free survival (15.7 months versus 11.1 months for sunitinib). The objective response rate was 60.6% for pembrolizumab plus axitinib and 39.6% for sunitinib. 

The researchers reported a variety of associations between the expression of biomarkers and outcomes (overall survival, progression-free survival, objective response rate). The biomarkers they evaluated included an 18-gene T-cell-inflamed expression profile, angiogenesis signature, and PD-1 ligand expression. 

“There is an unmet need for biomarkers that are predictive of patient outcomes following treatment with available first-line therapies for advanced renal cell carcinoma,” Rini said. “Although our analysis showed potential clinical utility of some RNA signatures in identifying patients who are likely to benefit the most from each treatment, further prospective clinical studies are needed.” 

Pembrolizumab plus axitinib is a first-line treatment option for patients with advanced renal cell carcinoma regardless of biomarker subtypes, he noted. 

The research was supported by the pharmaceutical company Merck Sharp & Dohme LLC, which played a role in the study design and conduct.

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The first class has completed the VERTICAL Program at Vanderbilt-Ingram Cancer Center, which provides medical and graduate school preparation for aspiring oncologists and cancer researchers.

The program was established in 2023 with financial support from the American Cancer Society, and Vanderbilt-Ingram had an inaugural class of four fellows. This was followed by the enrollment of another fellow in 2024.

“This is a two-year program that gives trainees a robust mentored research experience,” said Kimberly Dahlman, PhD, associate professor of Medicine, who is the assistant director of Research Education at Vanderbilt-Ingram. “In addition to being embedded in a cancer research laboratory, fellows also participate in professional development and cancer education activities, including career-path, lunch-and-learn sessions and cancer biology coursework.

“They are also involved in community service projects related to cancer. This program gives them dedicated time to prepare for their medical school or graduate school applications, in addition to their research experiences.”

In August, another class of four fellows will start the VERTICAL Program, which is kept small so it can be tailored to individual development plans. The participants do not receive credits toward graduate degrees, but they do become more competitive for acceptance into medical and graduate school programs.

“The VERTICAL Program gave me the final push I needed to pursue a PhD,” said Asia Miller, a member of the inaugural class from Indiana, who has a bachelor’s degree from Vanderbilt University in Biological Sciences “I was not confident in my identity as a researcher before the program, despite having done research in all four years of college. This was the best professional and personal development experience I have ever had.”

Bryan Hernandez, another inaugural class member who has a bachelor’s degree in Neuroscience from The University of Texas at El Paso, said he is looking forward to a career as a physician-scientist.

“The VERTICAL Program provided me with the perfect combination of structured mentoring and independent guidance throughout my two years in the program,” Hernandez said. “This dynamic exposed me to more robust career-building opportunities in areas of cancer research and medicine I was not previously familiar with. Thanks to my time in the VERTICAL Program, I was able to progress into the next formative step in my intended career path as a physician-scientist with a newfound outlook on the field of science and medicine I had been interested in.”

VERTICAL is an acronym for Vanderbilt Education Research and Training in Cancer and Leadership Program. It is open to individuals with bachelor’s degrees from nationally accredited colleges or universities who desire to pursue doctoral degrees and careers in science or medicine with a focus on cancer. Participants are paid a living wage.

“We also pay for MCAT preparation for fellows who want to take the MCAT for medical school applications,” said Dahlman, who is also co-director of the third- and fourth-year undergraduate medical education curriculum at Vanderbilt University School of Medicine.

VERTICAL fellows at Vanderbilt-Ingram are also offered the opportunity to do clinical shadowing and are provided financial support to attend one conference a year to present their research.

Vanderbilt-Ingram was selected as one of the five initial pilot locations for the postbaccalaureate fellows program, which was started by the American Cancer Society. Each of the pilot institutions has its own name for the program. Debra Friedman, MD, MS, holder of the E. Bronson Ingram Chair in Pediatric Oncology and deputy director of Vanderbilt-Ingram, serves as assistant director of the VERTICAL Program. Caroline Hartford is the senior program manager of VERTICAL.

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A new prospective clinical trial with updated data on COVID-19 hospitalizations and deaths among patients with cancer confirms the importance of vaccination and sheds light on which conditions put patients most at risk. 

Patients who had been vaccinated had a 50% reduction in risk of hospitalization, according to data from the National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS) published July 17 in JAMA Oncology.

Death incidence was highest in patients with lymphoma, intermediate in patients with acute leukemia and lung cancer, and lowest in patients with other solid tumors or with blood cancers other than lymphoma. Patients who had undergone chemotherapy or who had a history of stroke, atrial fibrillation and pulmonary embolism were at higher risk for hospitalization. 

The finding that patients with lymphoma had the highest risk of death suggests a potential detrimental effect of B-cell-depleting therapy on COVID-19 outcomes, the study stated, but the authors noted that this hypothesis was confounded by the inherent immunosuppression in patients with lymphoma. 

“These results are important because they represent the only prospective clinical trial in patients with a recent diagnosis of COVID and an active cancer undergoing therapy,” said the study’s lead author Brian Rini, MD, Ingram Professor of Cancer Research and Thomas F. Frist Sr. Professor of Medicine. 

Rini is one of two principal investigators of NCCAPS. The other is Lorissa Korde, MD, with NCI’s Cancer Therapy Evaluation Program, who is the study’s senior author. Patients were accrued for the study between 2020 and 2022, and the statistical analysis took place between September 2024 and April 2025. 

The study involved 1,572 adult patients who had a COVID-19 diagnosis within 14 days while receiving active treatment for cancer or had a prior stem cell transplant or CAR-T cellular treatment therapy. In addition to outcomes, investigators analyzed COVID-19 therapies patients received and disruptions in cancer treatment. The most common type of disruption was a delayed cancer treatment. 

The majority of patients had already been accrued for analysis before the Food and Drug Administration gave emergency use authorization for the antiviral treatment nirmatrelvir with ritonavir, which is most commonly known by its brand name, Paxlovid. Of the patients who enrolled in the study after the first COVID-19 vaccine received FDA emergency use authorization, 41.5% were fully vaccinated. 

“These data provide a road map to protect the most vulnerable cancer populations not only from COVID, but from potential future pandemics,” Rini said. 

Patients hospitalized for COVID-19 within 90 days of enrollment accounted for 18.4% of the study group. Among the hospitalized patients, 23.4% were admitted to an intensive care unit.  

The study was funded in part by the Coronavirus Aid, Relief, and Economic Security (CARES) Act, and also by the National Cancer Institute National Clinical Trials Network, Experimental Therapeutics Clinical Trials Network, and Community Oncology Research Program grants via the U10 funding mechanism.  

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Stand Up To Cancer (SU2C) has announced that its ninth biennial roadblock televised fundraising special will air on Friday, Aug. 15, from Nashville, bringing together country music stars, celebrities, athletes, cancer researchers and survivors for a powerful evening of inspiration and celebration.

This marks the first time the telecast will be broadcast from Nashville, and it will take place at The Pinnacle, a new premier event venue in the heart of Music City. Airing at 7 p.m. CT, the one-hour special continues SU2C’s 17-year mission to fund cancer research and save lives.

With the move to Nashville, SU2C will harness the city’s creative energy and musical heritage to bring a new dimension and excitement to this year’s show. The telecast will feature artists from country and other musical genres coming together in unique collaborations, an artistic reflection of SU2C’s commitment to scientific teamwork where researchers unite to accelerate progress.

Music icon Dolly Parton will appear in the special, with GRAMMY Award-winning artist Sheryl Crow serving as host. Additional performers and celebrity participants will be revealed in the weeks ahead.

Vanderbilt-Ingram Cancer Center is welcoming SU2C to Nashville.

“We are thrilled that Stand Up To Cancer will be bringing this special event to Nashville, and we welcome them to our city,” said Ben Ho Park, MD, PhD, Benjamin F. Byrd Jr. Professor of Oncology, professor of Medicine, and director of Vanderbilt-Ingram. “Our physicians, researchers and patients are familiar with the exceptional work of this organization that funds research to advance cancer treatments, which ultimately saves lives.

“This will be an extraordinary evening featuring some of Nashville’s most talented entertainers, and we hope everyone will join us for the telecast that will showcase not only our great city, but also the amazing research that has emanated from SU2C.”

As a leading academic medical center with deep roots in the region, Vanderbilt-Ingram shares SU2C’s commitment to advancing cancer research and improving patient outcomes.

“The goal of Stand Up To Cancer has always been about working collaboratively to push cancer research forward so we could help patients as quickly as possible,” said Katie Couric, SU2C co-founder. “Nearly two decades later, it’s incredibly gratifying and inspiring to see the impact of this research. Bringing the show to Nashville will infuse new energy and excitement into our mission. There’s still so much work to do and every dollar makes a difference — especially to the families who are counting on novel approaches and therapies as they face the challenges that often accompany a cancer diagnosis.”

The biennial special will be carried across more than 30 participating media platforms, including all four major U.S. broadcast networks, which are generously donating one hour of commercial-free primetime. Viewers will also be able to watch the telecast on-demand across multiple digital and streaming platforms, ensuring broad and flexible access to this one-night-only event.

Telecast viewers will hear from leading SU2C-funded researchers about recent advances and why continued support is vital in the fight against cancer. The program will also feature powerful stories from survivors who benefited from research made possible by donor contributions. From early detection to new treatment approaches, these stories reflect the real-world impact of SU2C-funded research and the hope it brings to patients and families.

Stand Up To Cancer was established in 2008 by a group of women who wanted to galvanize the entertainment community to raise awareness and funding to advance collaborative cancer research and end cancer as a leading cause of death.

Since its inception, SU2C has brought together over 3,100 top researchers from more than 210 leading institutions across 16 countries to collaborate on advancing cancer research.

SU2C-funded research has contributed to the saving of tens of thousands of lives worldwide.

To learn more about the 2025 event, visit https://standuptocancer.org. For more information visit StandUpToCancer.org, Instagram, TikTok, X, Facebook, and YouTube. 

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Susan G. Komen has awarded $10.8 million in new research grants that will help propel innovative science and deliver hope to those facing breast cancer. The grant recipients include three researchers from Vanderbilt University Medical Center.

The grants support 25 cutting-edge projects at 17 institutions — marking a powerful commitment to improving outcomes for people living with breast cancer today and in the future.

“We are proud to support these exceptional researchers who are pushing the boundaries of what’s possible in breast cancer science,” said Paula Schneider, president and CEO of Susan G. Komen. “Research saves lives, and now more than ever, we must invest in science that brings hope to patients — especially those facing the most aggressive forms of breast cancer.”

The three VUMC researchers were each awarded Komen Leadership Grants of $400,000. The Komen Leadership Grant Program supports innovative, hypothesis-driven breast cancer research that aligns with Komen’s mission to save lives and improve personalized care and outcomes for all. Open to Komen’s Scientific Advisors and to Komen Scholars, the program funds bold, high-risk/high-reward projects with the potential to significantly advance the field of breast cancer research.

The VUMC recipients are Tuya Pal, MD, Ingram Professor of Cancer Research and professor of Medicine; Ben Ho Park, MD, PhD, Benjamin F. Byrd Jr. Professor of Oncology and professor of Medicine; and Jennifer Pietenpol, PhD, Ingram Professor of Cancer Research and professor of Biochemistry.

Through this research investment, Komen is prioritizing the most pressing challenges facing patients, including metastatic breast cancer, optimal health for all and the need for more precise, personalized treatment strategies to improve care and outcomes for everyone impacted by breast cancer.

“Komen’s commitment to breast cancer research comes at a pivotal time and will drive meaningful advances in our understanding of the disease and care of patients,” said Ann Partridge, MD, MPH, Chief Scientific Advisor for Komen. “By fueling science that is both innovative and inclusive, we’re accelerating progress where patients need it most — while building a foundation for individualized care for all.”

Komen is the largest nonprofit funder of breast cancer research outside the U.S. government, investing nearly $1.1 billion since its inception. Unlike many research institutions, Komen’s work is powered entirely by the generosity of individual donors, corporate partners and community supporters.

“Investing in top scientific talent is one of the most powerful ways we can drive progress,” said Pietenpol, PhD, Chief Scientific Advisor for Komen. “Komen’s commitment, especially to early-career researchers, cultivates a vibrant ecosystem where bold ideas and pioneering research can thrive, accelerating our path toward the cures we urgently seek.”

Pietenpol holds the Brock Family Directorship in Career Development at VUMC. Park is director of the Vanderbilt-Ingram Cancer Center and a member of the Komen Scientific Advisory Board. Pal is a Komen Scholar.

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Cancer patients who scored lower on health literacy screening experienced higher all-cause mortality, according to a study published in the journal Cancer.

The study followed Vanderbilt-Ingram Cancer Center patients for a median of 3.1 years who had taken the Brief Health Literacy Screen. Patients who had high health literacy on the screening lived 9.4 months longer compared to those with low health literacy (score of nine or lower). The 9,603 patients in the retrospective cohort study were diagnosed with either prostate, lung, breast, renal, colorectal, brain, head and neck, bladder, pancreatic, liver, sarcoma or gastric cancer.

“Cancer care is extremely complex, and we highlight that health literacy is an important risk factor in terms of survival in one of the largest studies conducted evaluating the impact of health literacy and cancer survival,” said the study’s senior author, Kamran Idrees, MD, MSCI, MMHC, Ingram Professor of Cancer Research, professor of Surgery and chief of the Division of Surgical Oncology and Endocrine Surgery.

He further stated, “Since health literacy is a modifiable risk factor, it provides us an opportunity for real-time identification of patients with low health literacy to personalize care, provide health literacy sensitive resources, tailored instruction and education to improve their cancer care.”

The screening consists of three multiple-choice questions about patients’ comfort levels with understanding medical information and filling out hospital forms. A point system, ranging from one to five, is assessed according to answers to the questions.

Although the study did not seek to discover causal findings, such as direct links between patient mortality and patients’ ability to make informed decisions about treatment scenarios, the investigators surmised the difference in outcomes was likely multifactorial.

The investigators stated they endorsed the routine collection of health literacy information for patients diagnosed with cancer and that they encouraged the adoption of strategies to improve organizational health literacy in facilities that provide cancer care. They noted that not all cancer patients with low health literacy experienced worse outcomes. Observational studies for specific cancer types that assess health literacy are needed to evaluate interventions aimed at improving outcomes, they said.

Other Vanderbilt authors on the study included Kelvin Moses, MD, PhD, Julia Whitman, MS, and Sunil Kripalani, MD, MSc.

The investigators state that to their knowledge the study is the first to assess the association between health literacy and all-cause mortality among different cancer types.

The research received support from a Society of Surgical Oncology Foundation Investigator Award for a grant titled “Health Literacy and Cancer Outcomes.”

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A study published in the journal JAMA Surgery demonstrated the benefits of using fluorescence-guided imaging to assess margins in head and neck cancer. Researchers at Vanderbilt University Medical Center found that leveraging data collected both during surgery (in vivo) and after the tumor’s removal (ex vivo) can help guide surgeons in achieving a negative margin in cancer resection. 

A margin refers to the areas around the tumor being removed. The desirable outcome is to complete surgery with a negative margin, indicating that no cancer was found at the edge of the resection. A positive margin indicates that cancer cells remain in the tissue, which increases the risk of recurrence and reduces the chance of survival. 

To assess those margins, surgeons may use fluorescent agents administered to the patient’s tissue. Systemically infused agents have been shown to differentiate cancerous and healthy tissue with high accuracy. 

“Our research found that the use of fluorescence imaging both internally and externally can improve surgeons’ ability to precisely and safely excise tumors,” said Shravan Gowrishankar, MD, a research fellow in the Department of Otolaryngology-Head and Neck Surgery and the study’s first author. “This research seeks to illuminate methods of leveraging fluorescence imaging to achieve negative margins, particularly for deep resections, which often prove difficult.” 

The researchers defined two classifications of margins: the superficial or mucosal margin refers to the area uninvolved with the tumor but surrounding its surface, while the deep margin refers to the 4 to 5 millimeters of healthy tissue beyond the tumor’s most invasive points, or the depth of normal tissue between the tumor edge and the cut surface of the specimen. 

“Currently, it’s easier to achieve negative mucosal margins than deep margins,” said corresponding author Eben Rosenthal, MD, chair of the Department of Otolaryngology-Head and Neck Surgery and Barry and Amy Baker Professor of Laryngeal, Head and Neck Research. “Deep margins aren’t able to be assessed as easily because surgeons must rely on estimation of the distance from the tumor to guide the resection. 

“We sought to improve methods of achieving negative margins across the board because estimation isn’t good enough where patient safety is concerned.” 

The assessment of deeper margins is further confounded during surgery by tissue retraction and the presence of blood, which can obscure the view of the surgeon. And while autofluorescence — a process by which naturally occurring chemicals in the tissue can absorb light of a particular wavelength and reemit it at a different wavelength — can help surgeons assess mucosal margins, deeper margins are impossible to assess via this process because the light does not penetrate beyond a millimeter. 

To assist in ensuring a negative margin in a deep resection, surgeons can use fluorescence imaging techniques. Mapping tumors after resection can provide data on how close the margins are to the surface of the deep resection, and intraoperative in vivo fluorescence imaging can reveal areas of residual disease in the tumor bed. In combination, the information provided by both methods of fluorescence imaging can guide further examination and sampling to help achieve fuller resection of the deep margin. 

While both methods in combination are critical to achieving better outcomes in surgery, said Gowrishankar, ex vivo imaging devices have certain advantages over in vivo hardware. 

“While the data we get from in vivo imaging is valuable, it’s largely qualitative because of variance in ambient light in the operating room,” said Gowrishankar. “Ex vivo imaging is more precise because we can seal out external light in a controlled environment to measure fluorescence intensity and guide our assessment of deep margins.” 

In ex vivo imaging, fluorescence intensity increases the closer the tumor tissue approaches the cut surface of the tumor specimen, and data from this measurement can be used to create a sort of “heat map” measuring the relative depth of the tumor across the entire specimen. By using this imaging technique, surgeons can more precisely detect the reach of cancer cells in the tissue and perform precise resections. 

“Mucosal margins are easy enough to detect during surgery without fluorescent agents, but those agents are critical in helping us close the gap with deep margins,” said Rosenthal. “Missed deep margins contribute to the majority of positive margins after resection, which in turn contribute to negative health outcomes for patients. Large-scale adoption of these techniques will have a meaningful impact on the health of patients who undergo surgery to remove cancerous tumors.” 

Additional authors from Vanderbilt University Medical Center include: 

• Jennifer Choe, MD, PhD, assistant professor of Medicine in the Division of Hematology Oncology 

• Alexander Langerman, MD, SM, FACS, associate professor of Otolaryngology-Head and Neck Surgery 

• Kyle Mannion, MD, FACS, associate professor of Otolaryngology-Head and Neck Surgery 

• Aviva S. Mattingly, MD, MS, VTOPS/R25 Research Resident 

• Sarah L. Rohde, MD, MMHC, associate professor of Otolaryngology-Head and Neck Surgery and division director of Head and Neck Oncologic Surgery 

• Robert Sinard, MD, FACS, professor of Otolaryngology-Head and Neck Surgery 

• Hidenori Tanaka, MD, PhD, visiting assistant professor of Otolaryngology-Head and Neck Surgery 

• Michael Topf, MD, MSCI, assistant professor of Otolaryngology-Head and Neck Surgery. 

This research was supported by the National Cancer Institute, part of the National Institutes of Health (grants R01CA279249, R01CA239257, R01CA266233 and R01CA238686). 

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One person in 10 over the age of 70 will experience an explosive, clonal growth of abnormal blood cells, called clonal hematopoiesis of indeterminant potential or CHIP, that increases the risk of blood cancer and death from cardiovascular, lung and liver disease. 

The risk of blood cancer differs significantly, however, depending upon whether patients with CHIP also develop cytopenia (low blood cell count). 

An analysis of genetic sequencing data from more than 34,000 people over a 17-year period by researchers at Vanderbilt University Medical Center has found that persistent cytopenia appears to be a critical step in the progression of CHIP to blood cancer. 

For patients with CHIP who developed cytopenia, the risk of progression to blood cancer was 10 times higher than it was for patients without cytopenia — a 1-in-200 chance per year versus 1 in 2,000, the researchers report in the June 2025 issue of the Lancet journal, eClinicalMedicine.  

These findings suggest that checking blood counts regularly may be an effective way to monitor patients with CHIP for their risk of developing blood cancer, and cytopenia-free survival may be a valuable endpoint for clinical trials aimed at preventing blood cancer in these patients.

“This work is the largest longitudinal analysis of its kind and provides a roadmap for identifying high-risk CHIP patients who may benefit from closer monitoring or early intervention,” said the paper’s corresponding author, Alexander Bick, MD, PhD, associate professor of Medicine and director of the Division of Genetic Medicine at VUMC. 

“It also lays the groundwork for more feasible and targeted clinical trials in blood cancer prevention,” he said. 

Bick is internationally known for his research on the genetics of blood disorders. He and his colleagues have advanced the understanding of somatic (non-inherited) mutations in blood stem cells that can trigger a potentially life-threatening clonal growth of abnormal cells known as CHIP.  

Blood cancer (myeloid neoplasm) results from the abnormal growth of myeloid (blood) cells in the bone marrow. The current study compared blood cancer rates in patients with CHIP who did not develop cytopenia, to those with both CHIP and concurrent, clonal cytopenia of undetermined significance. 

Led by the paper’s first authors, James Brogan, MD, MS, a resident physician in the Department of Medicine, and Ashwin Kishtagari, MD, assistant professor of Medicine in the Division of Hematology and Oncology, the study required large numbers. 

The researchers pulled genetic sequencing data from three major population-level cohorts: the National Institutes of Health (NIH) All of Us Research Program, the UK (United Kingdom) Biobank and VUMC’s biobank, BioVU. 

With roughly 350,000 DNA samples collected to date, BioVU is the world’s largest repository of genetic material linked to de-identified electronic health records (EHRs) based at a single academic center.  

Access to whole genome sequences linked to EHRs for more than 107,000 adults enrolled in BioVU between 2006 and 2023 was provided through the Alliance for Genomic Discovery (AGD), a unique endeavor to accelerate the application of large-scale genomics to biomedical science and therapeutic development. 

Launched in 2022 by Nashville Biosciences LLC, a wholly owned VUMC subsidiary, and the global DNA sequencing giant Illumina Inc., AGD now includes eight major pharmaceutical companies that support the development and availability of whole genome sequences for research aimed at identifying disease associations and targets for intervention. 

The report in eClinicalMedicine “is one of the first papers to leverage data from the BioVU/Alliance for Genomic Discovery whole genome sequencing effort,” Bick said. “It also highlights how at VUMC medical trainees are doing cutting-edge research while developing as physicians.” 

Between the three biobanks, the researchers had access to 805,000 whole genome sequences. From this pool, they identified 8,114 individuals with CHIP who did not develop cytopenia and 1,260 who did. These 9,374 cases were matched with 24,749 controls who did not have CHIP. 

The annual blood cancer progression rate for participants with CHIP who did not develop cytopenia was nearly the same as the rate observed in the control population without CHIP (0.06% versus 0.04%), whereas the rate was 10 times higher for those with both CHIP and cytopenia (0.5% per year). 

Approximately 13% of participants with CHIP developed a cytopenia within five years. Men, smokers and older individuals (over 64) were at a higher risk of developing cytopenia, as were those who had two or more mutations or any high-risk mutations associated with CHIP. 

“Given the substantial risk of cytopenia, patients with multiple high-risk features may benefit from regular monitoring for cytopenia progression,” the researchers concluded. The good news is that this five-year window before the development of cytopenia and blood cancer “provides an opportunity for early intervention with potential disease-modifying therapies,” they wrote.  

Treatments for cytopenia range from drugs that stimulate the production of certain blood cell types to bone marrow or stem cell transplants. 

Co-authors from the Bick lab included rheumatology fellow Robert Corty, MD, PhD, Yash Pershad, an MD-PhD student, and Brian Sharber, MS. Other VUMC co-authors included faculty members Brett Heimlich, MD, PhD, Leo Luo, MD, Brent Ferrell Jr., MD, Michael Savona, MD, and Yaomin Xu, PhD. 

This research was supported by NIH grants DP5OD029586, R01AG088657, R01AG083736, and P30CA068485, the Burroughs Wellcome Fund Career Award for Medical Scientists, the Edward P. Evans Foundation, and the Pew Charitable Trusts and the Alexander and Margaret Stewart Trust. 

Savona holds the Beverly and George Rawlings Directorship. Bick is supported in part by a Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience Research, and Brogan is supported in part by an American Society of Hematology HONORS Award.

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An early-stage clinical trial, supported by the Department of Defense, has demonstrated that the targeted cancer drug trametinib shows potential as an interventional therapy to reprogram precancerous gastric lesions, potentially preventing them from becoming malignant, and that it can be administered safely.

The results of the Phase 1 trial involving 15 patients, which were published recently in Gastroenterology, were pleasantly surprising, said James Goldenring, MD, PhD, professor of Surgery and of Cell and Developmental Biology at Vanderbilt University Medical Center.

The primary goal of this trial was to evaluate whether a low-dose, limited duration treatment of two weeks with trametinib would be safe for patients at risk for developing a second cancer after having undergone resection of a Stage 1 gastric cancer. The drug also showed promise that it could be the first therapeutic intervention against precancerous lesions in the stomach.

Endoscopies revealed that trametinib reversed metaplasia, which is an abnormal change of cells into ones that are non-native to the tissue and can progress to dysplasia, an irreversible change in cell development that can lead to cancer. While the 15 patients in the study had no evidence of recurrent cancer, they did have extensive metaplasia when they entered the study.

“I was pleasantly surprised at how much benefit we could see in the endoscopies after one month and one year; it really was pretty remarkable,” said Goldenring, the Paul W. Sanger Professor of Experimental Surgery.

The reversal of the metaplasia could be viewed in endoscopic images and was confirmed with biopsies.

“I think that’s almost more compelling than anything else in this study,” Goldenring said. “I honestly did not expect endoscopies to be that different, but they were.”

However, he noted that follow-up clinical trials with more participants are needed to further validate the drug’s efficacy. The only significant side effect among the participants was one patient with a mild increase in blood pressure after trametinib treatment that returned to normal after the patient stopped taking the drug.

The patients in the study were recruited from Japan, where the clinical trial was led by Sachiyo Nomura, MD, PhD, in collaboration with Goldenring. Trametinib is an inhibitor of the MEK signaling pathway. MEK, an abbreviation for the mitogen-activated extracellular signal-regulated kinase pathway, plays an integral role in the development of stomach cancer.

The study was supported by a $2.5 million Department of Defense Translational Team Science Award, which is also supporting another clinical trial in the United States with similar aims. The U.S. clinical trial will evaluate the effectiveness of pyrvinium, an existing medicine that has been used for the past 70 years to treat pinworms in children, for a new purpose — reversing metaplasia of stomach cells and killing dysplastic precancerous cells. Pyrvinium also blocks the MEK pathway.

While stomach cancer is one of the three leading causes of cancer-related deaths worldwide, its incidence is lower is the U.S. Nevertheless, it does occur more frequently among minority ethnic groups, and incidence has been rising among young women. DOD support for clinical trials reflects the increased incidence of stomach cancer in minority groups, which make up a higher percentage of the U.S. armed services than of the general population. In the U.S., most stomach cancers are diagnosed at late stages when they are more difficult to treat.

Goldenring said he hopes the MEK inhibitor study will spur more research into therapeutic interventions for people with precancerous lesions who are at high risk for cancer.

“I’m hoping that this is a direction that multiple researchers might take in the future to really change the dynamics of how we’re going to intervene so that people don’t develop cancer,” he said. “That’s a different mindset than we’ve had previously.”

Eunyoung Choi, PhD, associate professor of Surgery and of Cell and Developmental Biology, is a co-principal investigator of the pyrvinium study along with Katherine Garman, MD, associate professor of Medicine at Duke University. Choi is also a co-author of the study published in Gastroenterology.

Goldenring is supported by grants from the Department of Defense, a Department of Veterans Affairs Merit Review Award, and the National Institutes of Health (R01DK101332 and R01CA272687. Choi is supported by grants from the National Institutes of Health (R37CA244970 and R01CA272687), the Department of Defense, the American Association for Cancer Research, and an American Gastroenterological Association Robert & Sally Funderburg Research Award.

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When 4-year-old Monroe Peterson was diagnosed with cancer, her family was determined to not only rally around her in support but also wanted to make a difference for other patients and families going through a similar experience.

To honor her journey, in November 2024 Monroe’s father, fitness expert and celebrity trainer Gunnar Peterson, started the MVP Challenge on his app, Common Ground, to raise awareness and funds for pediatric cancer efforts at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

The MVP Challenge, named for Monroe Vivian Peterson, included four weeks of guided workouts, question and answer sessions with Gunnar, and an opportunity to win special prizes. The fitness challenge raised funds to support pediatric cancer research, training and care at Monroe Carell.

“For months, Monroe has faced this battle with more grit, determination and positivity than I’ve ever seen,” said Peterson. “She hasn’t backed down; she doesn’t quit; and she moves forward with a smile on her face every day. To honor her strength, we launched the MVP Challenge as a way to come together as a community, push ourselves and raise funds to support children’s cancer treatment and research.”

Monroe was diagnosed with acute myeloid leukemia and completed two rounds of chemotherapy. She received two bone marrow transplants, one from each of her older brothers, and she is now in remission.

During her treatment, Monroe’s family says that she brought positivity, joy and levity to those around her and earned the nickname MVP. Many family members, friends and community members came together in support of the challenge to make it a success.

“We are blown away by the incredible success of the MVP Challenge and know that it would not have been possible without the advocacy, outreach and community engagement work of Gunnar, Jess and the whole Peterson family,” said Debra Friedman, MD, MS, director of the Division of Pediatric Hematology and Oncology at Monroe Carell, deputy director of Vanderbilt-Ingram Cancer Center, and holder of the E. Bronson Ingram Chair in Pediatric Oncology. “This challenge was a wonderful way to honor Monroe’s journey and tenacious spirit.”

Funds raised from the MVP Challenge will support Monroe Carell’s vision to advance personalized pediatric, adolescent and young adult cancer care in the region, specifically leukemia and stem cell research.

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