A Head and Neck Tumor Heterogeneity (HNTH) Laboratory, established at Ohio State in 2018, is studying the genetic makeup of tumor cells using patient-derived tumor models with living cancer cells. The goal is to better understand how intratumor heterogeneity develops, how to overcome its therapeutic challenges and how it might be turned into better targeted therapy.Lab founder James Rocco, MD, PhD, FACS, professor and chair of Ohio State’s Department of Otolaryngology – Head and Neck Surgery, in collaboration with Ed Mroz, PhD, Ohio State research associate professor, has developed a mutant allele tumor heterogeneity (MATH) tool based on next-generation sequencing that measures genetic changes in a cancer cell tumor. The researchers want to establish how different the genetic changes are among cancer cells in the same tumor.
Most of the tumors they study are head and neck squamous cell carcinomas originating in various subsites in the head and neck region. These include primary and recurrent tumors.
Dr. Rocco explains the significance of intratumor heterogeneity, saying, “In two retrospective studies, we determined that in tumors where most of the cells have the same changes, those tumors tend to respond very well to different types of therapy, whether it’s surgery, radiation or chemotherapy. On the other hand, if individual cancer cells within a tumor have a lot of genetic variation, that tumor doesn’t tend to respond well to therapy.”
Present data suggest that MATH values may help make difficult choices about the best regimen for an individual patient, in particular whether further treatment is needed following surgery and whether adding chemotherapy to radiation following surgery will provide survival benefits that outweigh the risks to patients’ long-term function and quality of life. Prospective clinical studies are planned to validate these applications.
“This genetic sequencing tool is really good at predicting who should and should not get radiation therapy after surgery,” Dr. Rocco says.
He adds, “The long-term goal is to understand what causes intratumor heterogeneity. If we can understand that, we can start to target it clinically to make a high-heterogeneity tumor act like a low-heterogeneity tumor.”
Contributing to a Bigger Picture
The HNTH Lab works closely with Ohio State’s Total Cancer Care® (TCC) Program, which is a founding member of the Oncology Research Information Exchange Network (ORIEN). Established in 2014 by The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Moffitt Cancer Center in Tampa, Florida, ORIEN is working to develop more precise ways to prevent, detect, diagnose and treat cancer.
ORIEN’s 18 members in North America use a single protocol, Total Cancer Care (TCC), when consenting new patients. TCC tracks clinical, molecular and epidemiological data throughout each patient’s lifetime. Partners have access to one of the world’s largest clinically annotated cancer tissue repositories and data. This allows them to share de-identified data so they can accelerate the development of targeted treatments and more quickly match eligible patients to clinical trials. Thus far, around 200,000 patients have consented to donate their tissue to ORIEN.
Director of the Head and Neck Tumor Heterogeneity Laboratory Bhavna Kumar, MS, explains that most patients give consent both to TCC/ORIEN and to HNTH for use of their tissue samples and clinical records. She notes, “TCC presently collects only frozen or preserved tissue specimens, which kills the cancer cells and makes some important types of studies impossible. We develop patient-derived tumor models from head and neck cancer patients in ways that keep cancer cells alive for these other types of studies. We provide excess tissue, cells, tumors or other samples to TCC for inclusion in the ORIEN network.”