On May 15, 2025 City of Hope Research Spotlight offers a glimpse at groundbreaking scientific and clinical discoveries advancing lifesaving cures for patients with cancer, diabetes and other chronic, life-threatening diseases (Press release, City of Hope, MAY 15, 2025, View Source [SID1234653196]). Each spotlight features research-related news, such as recognitions, collaborations and the latest research defining the future of medical treatment.
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This roundup highlights diabetes research, the role of obesity in multiple myeloma, results from a clinical trial of a new liquid biopsy for evaluating potential responses to epidermal growth factor receptor (EGFR) inhibitors in metastatic colorectal cancers, the discovery of a biomarker that could predict a patient’s response to immune checkpoint inhibitors, a scientific statement from the American Heart Association on addressing cardiovascular toxicity in patients who had pediatric cancers and a study of a new medication that helps stop leukemia cells from decreasing the activity of the immune system.
To learn more about research at City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States, with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report, subscribe to City of Hope Research Spotlight.
HIRN Closes the Gap Between Vision and Victory in Type 1 Diabetes
A new report highlights the remarkable advances made in type 1 diabetes research since the National Institute of Diabetes and Digestive and Kidney Diseases established the Human Islet Research Network (HIRN) in 2014.
Lead author John Kaddis, City of Hope associate professor in the Department of Diabetes and Cancer Discovery Science within the Arthur Riggs Diabetes & Metabolism Research Institute, and members of the HIRN reflect on the past, present and future of type 1 diabetes research. The HIRN was formed to bring together experts from around the world to solve intractable problems in type 1 diabetes.
The article describes the milestones, achievements and critical goals of type 1 diabetes research, including:
Pioneering advances, technologies and systems that uncover the interactive role of insulin-producing beta cells within their physiological environment.
Innovative tools, disease models, devices and strategies that promote novel discoveries.
Shared resources, data access and interdisciplinary training to challenge scientific dogmas.
Although significant progress has been made, Kaddis emphasizes that successful approaches to preventing type 1 diabetes are still in their infancy. Kaddis and colleagues point out knowledge gaps in the processes underlying human beta cell loss, protection and replacement in type 1 diabetes.
Contributions by the HIRN are expanding scientific knowledge about the causes of type 1 diabetes and expediting the development of effective strategies to prevent, diagnose and treat the disease, the authors concluded.
For more information, see the journal article in Diabetes.
Exploring the role of obesity in progression from precursor condition to multiple myeloma
Patients with multiple myeloma incur some of the highest costs in cancer care to manage their disease. So, it’s imperative that people with a precursor condition called monoclonal gammopathy of undetermined significance (MGUS) know the risk factors that make progression to myeloma more likely.
To learn more about the role obesity plays in MGUS progression to cancer, a team led by Lawrence Liu, M.D., clinical fellow in hematology and medical oncology at City of Hope, and co-authors Murali Janakiram, M.D., M.S., of City of Hope and Su-Hsin Chang, Ph.D., of Washington University School of Medicine, which reviewed body mass index measurements over time in a cohort of nearly 22,500 people with MGUS.
The team’s findings, published recently in JAMA Network Open, suggest that maintaining a healthy weight may prevent MGUS from developing into myeloma. Using data collected about the patients by the U.S. Veterans Health Administration, the researchers tracked exposure to elevated body mass index for three years post-MGUS diagnosis.
Of the study participants, 21.7% had a healthy BMI between 18.5 to less than 25 at baseline. For this population, an increase of elevated BMI over time was associated with a higher risk of progression. Participants whose baseline BMI was 25 or greater had a 17% to 27% higher risk of progression to myeloma compared with patients with baseline BMI within the reference range. The researchers believe this cohort study is the first to quantify the association between cumulative exposure to BMI 25 or greater and the progression from MGUS to myeloma.
For more information, see the JAMA Network Open paper.
Predicting outcomes of EGFR inhibitors in metastatic colorectal cancer
In a recent paper published in Clinical Cancer Research, researchers from City of Hope, including corresponding author Ajay Goel, Ph.D., professor and chair of the Department of Molecular Diagnostics and Experimental Therapeutics, reported on outcomes from a clinical trial of a test to predict responses to certain medications in metastatic colorectal cancer (mCRC) patients.
The EXOsome and cell-free miRNAs of anti-EGFR ResistAnce (EXONERATE) interventional study developed, tested and validated a liquid biopsy to see how well it predicted progression-free survival, overall survival and objective response rate for two, first-line EGFR inhibitors — panitumumab or cetuximab — in mCRC.
Chemotherapy-naïve mCRC patients with certain genes (RAS wild-type) known to respond to EGRF inhibitors were recruited for two nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The EXONERATE assay was developed using a technology called genome-wide small RNA sequencing to identify candidate biomarkers to predict good versus poor responders to the medications.
There can be different responses to treatment based on where the primary tumor is located in patients with mCRC — the disease is characterized as either right-sided or left-sided — so the researchers tested and validated the assay in both populations. They reported that the EXONERATE assay was successful at robustly predicting progression-free survival and overall survival outcomes in patients with mCRC, both right- and left-sided, before they received either panitumumab or cetuximab.
For more information, see the Clinical Cancer Research paper.
Searching for biomarkers to assess likely immune checkpoint inhibitor response
Immune checkpoint inhibitors, which block certain proteins that suppress the immune system so that their body can better fight cancer, have changed the landscape of cancer therapy in recent years. But because many patients do not see long-lasting benefits, better biomarkers are needed to assess likely response rates in patients.
Recently, a team of researchers led by Kelly Mahuron, M.D., an assistant clinical professor of surgical oncology at City of Hope, sought to pinpoint biomarkers for a positive response to a certain type of immune checkpoint inhibitors called PD-1 pathway inhibitors. Building on prior knowledge that CD8+ tumor infiltrating lymphocytes (TILs) have been associated with PD-1 inhibitor response, they aimed to identify the subpopulations that have the most prognostic value.
In a paper published in Cancer Research, Dr. Mahuron and other authors outlined a series of experiments to search for predictive biomarkers in 129 tumor samples from melanoma patients. Through studies that included single-cell analysis, the team found that advanced melanoma patients with more than or equal 20% of CD8+ TILs that co-expressed PD-1 proteins and CTLA-4 protein receptors (which they call CPHi TILs) had better objective response rates and survival following PD-1 monotherapy than those below this threshold. Based on these results, they believe the biomarker assay they developed can be used to predict an immune checkpoint inhibitor response.
The team utilized single cell RNA sequencing to further characterize CPHi TILs and they found that this cell population contains a diverse mix of subpopulations. Their findings have important implications for optimizing checkpoint-based immunotherapy across other cancers.
For more information, see the Cancer Research paper.
Addressing Heart Health in Pediatric Cancer Survivors
While pediatric patients represent just roughly 5% of new cancer cases each year, this population has high survival rates, making them vulnerable to therapy-related cardiovascular disease later in life. To highlight recent advances in the growing field of cardio-oncology, a group of committee members from the American Heart Association, including vice-chair Saro Armenian, D.O., M.P.H., the Barron Hilton Chair in Pediatrics and the director of the Childhood, Adolescent and Young Adult Survivorship Program, recently issued a scientific statement in the journal Circulation that offers updates on emerging concepts related to established cardiotoxic therapies.
The authors note that an increasing recognition that nearly all cancer treatments can pose risks for future cardiovascular disease has led to close investigations of anthracycline chemotherapy and chest-directed radiotherapy. As a result, dose reduction, use of cardioprotection for anthracyclines, and modern radiotherapy approaches have contributed to improved cardiovascular outcomes for survivors.
The statement includes considerations for newer treatments, such as small-molecule inhibitors and immunotherapies, that have expanded options for some patients but also revealed new cardiotoxic challenges. In addition, Dr. Armenian and the committee members focused on issues related to transition of care after cancer treatment, including surveillance and prevention strategies, examined the role physical activity should play in rehabilitation after pediatric cancer care, and provided updates on how to manage cardiovascular complications.
By incorporating new strategies in an equitable manner, the authors say adult cardiologists can help improve the transition from pediatric to adult care and greatly influence long-term health-related outcomes for childhood cancer survivors who are at risk for cardiovascular disease.
To read the entire statement, see the review paper in Circulation.
Keeping leukemia growth in check
For patients with chronic myeloid leukemia (CML), a goal of treatment is to keep the disease from progressing to a blast crisis (BC) or acute phase, in which the cancer becomes more aggressive. The mechanisms of transformation to the BC phase are not fully understood, but recent research led by Bin Zhang, Ph.D., associate professor in the Department of Hematologic Malignancies Translational Science, and Guido Marcucci, M.D., professor and chair of the Department of Hematologic Malignancies Translational Science, has revealed a new pathway that enables leukemia cells to decrease the ability of the immune system to fight CML growth.
A paper in Nature Communications unveils how an acquired deficit of a microRNA called miR-142 can cause the loss of T cells that play a crucial role in attacking cancer as CML progresses to the BC phase. In addition, the miR-142 mutation allows leukemic stem cells to evade the immune system and further promote disease growth.
However, the researchers also found that an miR-142 deficit can be promptly mitigated using a synthetic miR-142 mimic designed and synthesized at City of Hope called M-miR-142. Used alone or in combination with certain monoclonal antibodies and/or tyrosine kinase inhibitors, M-miR-142 extended survival in mouse models with BC CML.
According to the study, the experimental findings add important insights to the mechanisms of BC transformation and may offer conceptually new treatment strategies. A wide range of preclinical studies for M-miR-142 are underway, as the team hopes for a rapid translation of their findings from bench to bedside.