Personalized medicine research for aggressive abdominal cancers at Wake Forest Baptist Health received a boost from a $2.5 million grant from the National Cancer Institute that supports research efforts at Wake Forest Organoid Research Center (WFORCE), a joint effort between the Wake Forest Baptist Comprehensive Cancer Center and the Wake Forest Institute for Regenerative Medicine (WFIRM) to tailor personalized therapy for patients.
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.
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