Cancer of the appendix is rare, affecting only 1 in 100,000 people in the United States annually. However, because it’s so rare, there’s limited research to help guide treatment decisions. But now, researchers at Atrium Health Wake Forest Baptist’s NCI-designated Comprehensive Cancer Center hope to change that with support from a $2.5 million grant from the National Cancer Institute.
“Because the appendix is part of the gastrointestinal system, appendiceal cancers have traditionally been treated in the same way as colon cancer,” said Lance Miller, associate professor of cancer biology at Wake Forest School of Medicine and co-principal investigator of the study. “However, we’re learning that these cancers are molecularly very different. By increasing our molecular understanding of appendiceal cancer, we hope to have greater insight on how best to treat, which will lead to better outcomes.”
According to Miller, appendiceal cancer is often diagnosed at late stages when it has already spread throughout the peritoneal cavity, the space within the abdomen that contains the stomach, liver and intestines. As a result, current treatment options are limited.
One treatment for patients with appendiceal tumors with spread to the peritoneal cavity is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). The CRS/HIPEC procedure involves surgically removing the cancerous tumors followed by the administration of heated chemotherapy directly into the abdomen to kill any residual cancer cells.
Wake Forest Baptist Medical Center was among the first hospitals in the U.S. to offer the procedure in 1991. The program is led by Dr. Edward Levine, professor of surgical oncology at Wake Forest School of Medicine and co-investigator of this study.
“A major challenge is that some patients respond well to CRS/HIPEC, and some do not,” said Dr. Konstantinos Votanopoulos, professor of surgery and director of the 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. “CRS/HIPEC is an aggressive, yet often effective, treatment in prolonging survival, but we don’t know how patients will respond ahead of time.”
Votanopoulos, who is also a co-principal investigator of the study, said the grant will support three objectives. One, researchers will build on previous research to develop a genetic test that will help identify patients who will benefit from CRS/HIPEC. Two, researchers will study gene expression patterns of high-grade tumors and how they impact survival. And three, the grant will support the use of patient-derived tumor organoids to study how mutations in the cancer might make a tumor more sensitive or resistant to certain chemotherapy drugs.
The creation of an organoid begins with a tissue biopsy of a tumor. Cells from this biopsy are then used to grow three-dimensional, patient-specific tumor organoids in the lab. By exposing the organoids to various chemotherapy drugs and observing their response, scientists can possibly predict how a patient will respond to treatment.
“This research has the potential to create new possibilities for personalized medicine in the treatment of appendiceal cancer,” Miller said.
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