Grant-funded research aims to advance adrenocortical carcinoma therapies

Posted: January 23, 2023

Adrenocortical carcinoma is a rare and aggressive cancer of the adrenal glands with a less than 6% five-year survival rate and no effective treatments.

Assistant Professors Jennifer Leight and Aleksander Skardal stand inside a research lab in Fontana Laboratories.
Assistant Professors Jennifer Leight (left) and Aleksander Skardal lead a multidisciplinary research project to create accurate preclinical research models for the progression of adrenocortical carcinoma.

According to researchers, the lack of new targeted therapies for adrenocortical carcinoma is primarily due to the absence of research models that accurately represent the disease.

Biomedical Engineering Assistant Professors Aleksander Skardal and Jennifer Leight lead a multidisciplinary team of Ohio State University researchers that received a $400,000 grant from the National Cancer Institute to create accurate preclinical research models for the progression of adrenocortical carcinoma (ACC).

Their work will utilize Skardal’s innovative organoid and metastasis-on-a-chip technologies to understand how ACC tumors progress. Organoids are 3D in vitro cultures that can be used to study complex signaling pathways, drug sensitivity, tumor cells and tumor progression.

These models overcome many issues associated with current cell lines and mouse models, Skardal said, but until now have not been used in adrenocortical carcinoma.

“As a result of our unique access to rare adrenocortical carcinoma samples and our expertise in adrenocortical carcinoma biology and organoid platforms, we have developed the first patient-derived tumor organoid model of ACC,” he explained. “This novel preclinical model, combined with the deployment of a new biosensor, will broaden our understanding of ACC molecular biology and lead to informed use of targeted therapies not only for the treatment of this devastating disease, but across a variety of solid tumors.” 

Joining Skardal and Leight as co-principal investigators is Dr. Priya Dedhia, an assistant professor of surgical oncology, a surgeon, and an expert in ACC biology, whose lab also uses organoid technology. The team also includes co-investigator Katherine Miller, a principal investigator at the Institute for Genomic Medicine at Nationwide Children’s Hospital and research assistant professor of pediatrics at Ohio State, who has expertise in cutting-edge genetic sequencing.

The project builds on the researchers’ extensive experience generating organoids for numerous tumor types, including for appendiceal cancer, colorectal cancer and lung cancer.

Skardal and Dr. Dedhia are co-founders and co-directors of the Ohio State Organoid Technology Program—composed of more than 30 faculty members from across the university who utilize organoid and organ-on-a-chip technologies or complementary technologies. This collaboration between several early career investigators led to a 12-month internal Cancer Biology Program Seed Award, federal funding and preliminary data for this research.

“Our ultimate goal is to deploy patient-derived organoid and organ-on-a-chip technology as a diagnostic tool that can be used to predict which treatments will work best for individual patients and drive subsequent therapies,” Skardal explained. “We believe that this is feasible within several years for some types of cancers.”

A member of the Ohio State faculty since 2019, Skardal’s research focuses on developing and using customizable biomaterials and biofabrication techniques to create tissue and tumor model systems for drug and toxicology testing, personalized oncology, and to explore biological phenomena such as tumor growth and metastasis.

Leight joined Ohio State in 2014 and investigates remodeling of the tumor microenvironment and the impact on cancer drug treatment using 3D fluorescent peptide sensors.

by Candi Clevenger, College of Engineering Communications, clevenger.87@osu.edu

Categories: ResearchFaculty