Cancer Chip Accurately Predicts Patient-Specific Chemotherapy Response

Esophageal adenocarcinoma (EAC), one of the two primary types of esophageal cancer, ranks as the sixth leading cause of cancer-related deaths worldwide and currently lacks effective targeted therapies. The standard treatment relies on chemotherapy, typically administered before surgery as neoadjuvant chemotherapy (NACT), with the aim of reducing or controlling tumor growth. However, many patients develop resistance to specific NACT regimens, which leads to poor prognoses. Due to the absence of viable alternatives, both responders and non-responders often continue receiving available chemotherapies without knowing if they will be effective. Even for those who initially respond, the chosen chemotherapy may not fully halt tumor progression or prevent metastasis, and it frequently causes harmful side effects. A major unmet clinical need is the development of a personalized, patient-specific precision oncology tool capable of accurately forecasting individual responses to different NACTs in a timely manner.

Previously, scientists developed “organoids” from biopsied EAC cells—3D miniature esophageal tissues formed from tissue-specific stem cells that replicate essential characteristics of the esophageal epithelial lining. Yet, these organoids lack vital elements of the tumor microenvironment (TME), such as stromal fibroblasts and collagen structures, and therefore do not accurately mimic how real tumors respond to NACT. Now, a new collaboration between the Wyss Institute for Biologically Inspired Engineering at Harvard University (Boston, MA, USA) and McGill University Health Centre (Montreal, Canada) has led to a promising personalized medicine solution aimed at improving chemotherapy outcomes for EAC patients. The team utilized the Wyss Institute’s human Organ Chip microfluidic culture technology to co-culture patient-derived EAC organoids alongside stromal cells collected from the same biopsies, which were obtained by the McGill team as part of a clinical cohort study. This approach resulted in patient-specific Cancer Chip models that include essential components of the TME.

These images illustrate how precision oncology Organ Chips recapitulate individual patients’ responses to chemotherapy (Photo courtesy of Wyss Institute at Harvard University)

By reconstructing key aspects of the TME in vitro, the researchers significantly enhanced the accuracy of predicting how a patient’s tumor would respond to standard NACT, outperforming the traditional, simpler 3D organoid models. The method delivers results within 12 days from model initiation, allowing for the timely stratification of EAC patients into likely responders and non-responders. It also supports the testing of alternative NACTs using different chemotherapeutic agents for patients showing resistance—all within a clinically actionable timeframe. These findings have been published in the Journal of Translational Medicine.

“This patient-centered approach strongly builds on our previous successes using human Organ Chip technology to recapitulate each individual cancer patient's TME outside their body so that we can identify the drug combination that will work best for that very patient. This new way to approach personalized medicine could be implemented at clinical centers focusing on the care of patients suffering from many different types of cancer, such as the one run by our collaborators with patients who have esophageal cancer,” said Donald Ingber, M.D., Ph.D., Founding Director at the Wyss Institute, who led the research. “Perhaps equally important, it can also be used as a pre-clinical testbed to break new ground in the development of tumor- or stroma-targeted therapies for cancer patients and enable the discovery of biomarkers that could be used to monitor and optimize drug effects in these patients."

Related Links:
Wyss Institute
McGill University Health Centre