$2.5M award to fund joint organoid research program at Wake to treat aggressive cancers

The funding supports development of a new drug testing platform to predict treatment outcomes for patients. The platform leverages tissue bioengineering advances and genomic technologies to reconstruct and grow patient-derived tumor organoids (i.e., fragments of a patient’s cancer) in the presence of different drugs to predict clinical responses of patients and guide treatment selection.

Creation of an organoid begins with a tissue biopsy of the tumor. Cells from this biopsy are then used to grow small tumors called “organoids” in the lab which behave similarly to the original tumor. The organoid model can accurately represent what occurs inside a patient’s body. Lastly, the best chemotherapy treatment is chosen by exposing the organoids to the various potential treatments and observing their response.

Konstantinos Votanopoulos, M.D., Ph.D., professor of surgery and director of WFORCE, and Lance D. Miller, Ph.D., associate professor in cancer biology, are the principal investigators of the grant, with Shay Soker, Ph.D., chief science officer and WFIRM professor, as a co-investigator.

WFORCE, which brings together researchers and clinicians to leverage the use of tissue organoid technology to tailor personalized therapy for patients, was formed in early 2020. To be awarded a competitive R01 grant of this size speaks to the need and transformational potential of WFORCE which combines world class multi-disciplinary clinical trial and patient care expertise through the NCI-designated Wake Forest Baptist Comprehensive Cancer Center and ground-breaking innovation and technology through WFIRM.

“Every time cancer cells multiply, they generate the next generation of cancer cells with new properties,” Votanopoulos said. “As the cancer progresses, the patient ends up with not just a single tumor, but many different tumor clones with variable biologic behavior and response to treatment. Accurate mapping of tumor clonality, combined with response of each clone to therapy is the key for the development of personalized treatment strategies tailored to each patient separately.”

Specifically, the research will look at determining clonality-based treatment response of high prevalence cancers such as colon, as well as very rare cancers with incidence less than 1 per 100,000 patients, such as appendiceal, that have spread throughout the abdomen where they grow as metastatic lesions on the surfaces of different organs.

“How patients respond to treatment varies widely, and this represents a major clinical challenge our grant seeks to address,” Miller said. “This genetic variation that occurs when the cancer cells multiply is believed to explain why most, but not all of a patient’s cancer can initially respond well to chemotherapy, but eventually return in a drug-resistant form.”

Soker said the project will generate new knowledge of how certain mutations, alone or in combination, impact response to specific drugs, adding that results of these studies will be leveraged in a future clinical trial.

Other key personnel on the grant are surgeon Edward A Levine, MD, pathologist Stacey O’Neill, MD, tumor immunologist David Soto-Pantoja, MD, and bioinformatics expert Guangxu Jin, MD.

About the Comprehensive Cancer Center: The center is designated by the National Cancer Institute (NCI) as a comprehensive cancer center, one of three in North Carolina, and one of 51 in the country and has held this designation continuously since 1990. The designation recognizes Wake Forest for the highest levels of expertise and a commitment to patient care, cancer research, including clinical trials, and education. The rapid pace of discovery and the early availability of many new cancer treatments at NCI-designated Comprehensive Cancer Centers, gives us an advantage in offering our cancer patients early access to the latest therapies and treatment options, sometimes even months or years before non-NCI cancer centers. Wake Forest has a team of 120 clinicians representing all aspects of cancer care including those in the fields of hematology and oncology, gynecologic oncology, radiation oncology, surgical oncology and colon and rectal surgery. 

About the Wake Forest Institute for Regenerative Medicine: The Wake Forest Institute for Regenerative Medicine is recognized as an international leader in translating scientific discovery into clinical therapies, with many world firsts, including the development and implantation of the first engineered organ in a patient. Over 400 people at the institute, the largest in the world, work on more than 40 different tissues and organs. A number of the basic principles of tissue engineering and regenerative medicine were first developed at the institute. WFIRM researchers have successfully engineered replacement tissues and organs in all four categories – flat structures, tubular tissues, hollow organs and solid organs – and 15 different applications of cell/tissue therapy technologies, such as skin, urethras, cartilage, bladders, muscle, kidney, and vaginal organs, have been successfully used in human patients. The institute, which is part of Wake Forest School of Medicine, is located in the Innovation Quarter in downtown Winston-Salem, NC, and is driven by the urgent needs of patients. The institute is making a global difference in regenerative medicine through collaborations with over 400 entities and institutions worldwide, through its government, academic and industry partnerships, its start-up entities, and through major initiatives in breakthrough technologies, such as tissue engineering, cell therapies, diagnostics, drug discovery, biomanufacturing, nanotechnology, gene editing and 3D printing.