Laboratory Research
Our laboratory and collaborative research programs investigate how to make cancer treatment more effective and less harmful. We link studies of cancer biology with drug development, patient genomics and clinical research to address questions that arise in caring for children and young adults.
Drug discovery and precision therapies for leukemia
We investigate the biological pathways that allow cancer cells to grow, survive and resist therapy. By combining molecular profiling with laboratory models and drug-response studies, we seek to identify vulnerabilities that can be targeted with new medicines or new uses of existing drugs.
A major focus is acute myeloid leukemia, particularly disease that returns after treatment or does not respond to initial therapy. In collaboration with leukemia investigators and drug-development teams, we are advancing strategies that target RAS signaling, inflammatory pathways, cancer metabolism and RNA regulation. Priorities include rational combinations of targeted agents with treatments such as azacitidine and venetoclax. These studies aim to identify which combinations merit clinical testing and which biological features may predict benefit or resistance.
Our work connects drug discovery with early-phase clinical trials. Findings from patient samples help refine laboratory hypotheses, while laboratory results inform treatment selection and the design of subsequent studies.
Pharmacogenomics and individualized cancer treatment
Inherited genetic differences can influence how the body processes anticancer drugs and how healthy tissues respond to treatment. Our pharmacogenomics research examines how these differences relate to treatment effectiveness, immediate side effects and complications that may emerge years later.
Using biospecimens and clinical information from cooperative-group studies, we seek genetic markers that could guide drug selection, dosing and supportive care. The long-term goal is to match treatment to both the cancer’s vulnerabilities and the patient’s capacity to tolerate therapy.
Hodgkin lymphoma genomics and lifelong health
Hodgkin lymphoma is highly curable, but some survivors experience serious treatment-related health problems. Our research seeks to understand why patients receiving similar therapies can have very different outcomes, with an emphasis on preventing long-term complications while preserving cure.
A planned expansion of this work will use germline whole-genome sequencing in approximately 1,000 children and adolescents from the Children’s Oncology Group AHOD0031 study. By examining inherited variation across the genome alongside treatment and outcome data, we aim to discover genetic factors associated with response, toxicity and late effects, including organ injury and subsequent cancers. Genetic susceptibility to Hodgkin lymphoma is a secondary area of investigation.
This work is intended to inform future risk-adapted clinical trials and survivorship strategies that account for an individual’s inherited biology.
Artificial intelligence and computational oncology
An emerging collaborative direction uses artificial intelligence and computational modeling to connect cancer genomics, inherited genetic variation, laboratory drug testing and clinical outcomes. We are developing research approaches to identify patterns that may help explain treatment response and toxicity and prioritize promising therapies for further study.
One goal is to develop patient-specific models, sometimes called digital twins, that can test hypotheses about how different treatment strategies might perform. These models require validation in independent datasets and prospective studies before they can support clinical decisions. Our emphasis is on generating testable predictions and understanding their limits, with applications being developed in leukemia and Hodgkin lymphoma.
Proton FLASH and radiation biology
Dr. Perentesis helps lead a multidisciplinary proton therapy research program with colleagues in radiation oncology, medical physics and cancer biology. A central focus is proton FLASH, an investigational approach that delivers radiation at ultra-high dose rates. The research asks whether this approach can preserve cancer control while reducing injury to healthy tissues.
Cincinnati Children’s and University of Cincinnati collaborators led FAST-01, the world’s first clinical trial of proton FLASH, and FAST-02, which extended this research to painful bone metastases in the chest. These early studies in adults established clinical feasibility and provided encouraging evidence of pain relief and tolerability. Further research is needed to determine whether FLASH reduces toxicity compared with conventional radiation delivery and how it can be used safely in children.
Our collaborative translational priorities include understanding the biological response to FLASH and evaluating tumor control alongside effects on normal tissues. This work is helping build the scientific foundation for future studies in pediatric and young adult cancers.
Connecting targeted therapy with immune and cellular approaches
Through collaborations across the Cancer and Blood Diseases Institute, we seek opportunities to combine targeted medicines, immune and cellular therapies, and radiation. Research priorities include understanding how these treatments affect the tumor environment and whether carefully selected combinations can overcome resistance. These efforts connect the lab’s interests in drug response and cancer biology with the institution’s broader immunotherapy and radiation programs.
Collaboration and translation to clinical trials
Our research brings together investigators in oncology, experimental hematology and cancer biology, genetics, pathology, pharmacology, computational science and radiation oncology. Collaborations across Cincinnati Children’s, the University of Cincinnati and national research networks connect our laboratory studies with well-characterized patient cohorts and clinical trials. This shared
