Organ Chip Technology Offers Precise Prediction of Chemotherapy Response in Esophageal Adenocarcinoma Patients
Harvard University and McGill University researchers develop personalized cancer chips to improve treatment outcomes
Esophageal adenocarcinoma (EAC), a leading type of esophageal cancer and the sixth deadliest cancer globally, has long posed a significant challenge to effective treatment. Currently, no targeted therapies exist for EAC, and patients typically undergo neoadjuvant chemotherapy (NACT) prior to surgery in hopes of shrinking tumors. However, the variability in patient responses often results in chemotherapy resistance, poor prognoses, and toxic side effects. Identifying which chemotherapy regimens will be effective for individual patients remains an unmet clinical need.
A breakthrough study led by Dr. Donald Ingber of the Wyss Institute for Biologically Inspired Engineering at Harvard University, in collaboration with Dr. Lorenzo Ferri of the McGill University Health Centre, now demonstrates that cutting-edge organ chip technology can accurately predict patient-specific responses to chemotherapy, potentially revolutionizing personalized oncology care for EAC.
Overcoming Challenges of Current Models
Traditional approaches relied on growing patient-derived "organoids," three-dimensional structures created from esophageal cancer stem cells that mimic some aspects of the tumor. However, these organoids lack critical components of the tumor microenvironment (TME)—including stromal fibroblasts and extracellular matrix elements like collagen—that influence cancer growth and chemotherapy response. This omission limited the organoids’ predictive power.
Leveraging the Wyss Institute’s advanced human Organ Chip microfluidic culture platform, the researchers developed a novel Cancer Chip model. This platform facilitates co-culture of EAC organoids alongside stromal cells isolated from the same patient biopsies. By recreating the tumor microenvironment in vitro, including cell-to-cell communication and fluid flow that mimics physiological conditions, this personalized model more accurately replicates tumor behavior and drug response.
Rapid and Accurate Prediction of Chemotherapy Response
The research team obtained biopsy samples from newly diagnosed EAC patients before treatment. The cells were used to generate personalized organoids and tumor-associated fibroblasts that were then seeded into adjacent microchannels separated by a porous membrane inside a chip the size of a memory stick. This setup enabled molecular exchange between cancer and stromal compartments. A chemotherapy drug cocktail, modeled after clinical regimens, was introduced to mimic patient treatment.
Results from a cohort of eight patients revealed remarkable accuracy, with Cancer Chips successfully predicting whether tumors would respond or resist chemotherapy within just 12 days. For half of the patients, the chip showed effective tumor cell death consistent with clinical response, while for the other half, it indicated chemotherapy resistance that correlated with poor patient outcomes after surgery.
Implications for Precision Oncology and Future Research
“This patient-centric approach builds on previous success using Organ Chip technology to simulate individual tumor microenvironments, helping to identify the best drug combinations for each patient,” stated Dr. Ingber, who is also Judah Folkman Professor of Vascular Biology at Harvard Medical School. He envisions broader applications of this technology for various cancers and its potential to accelerate discovery of tumor- and stroma-targeted therapies.
This personalized EAC Cancer Chip not only enables rapid stratification of responders versus non-responders but also offers a platform to test alternative chemotherapies for resistant patients within a clinically actionable timeframe. Such precision tools could reduce unnecessary toxic treatments for non-responders and guide oncologists in tailoring therapies for improved patient survival and quality of life.
Building on Prior Work in Esophageal Disease Modeling
The collaboration between Ingber’s and Ferri’s teams builds on earlier studies modeling Barrett’s esophagus—a precancerous condition characterized by abnormal esophageal tissue changes linked to acid reflux and inflammation—using Organ Chip technology. This foundational work elucidated how pathological shifts in epithelial and stromal cells contribute to esophageal cancer progression, enabling the group to advance directly to modeling the full cancer microenvironment.
Funding and Acknowledgments
This research was published in the Journal of Translational Medicine and supported by a Cancer Research UK Grand Challenge STORMing Cancer grant, focusing on the role of stroma in disease pathology, as well as funding from the Montreal General Hospital Foundation and Impact Grant awards.
The investigative team included members from both Harvard and McGill facilities, such as Dr. Elee Shimshoni, Dr. Sanjima Pal, Salvador Flores Torres, Mingyang Kong, and others who contributed to this significant advancement.
References:
Ingber, D. et al. (2025). Patient-specific Esophageal Adenocarcinoma Cancer Chips Accurately Predict Response to Neoadjuvant Chemotherapy. Journal of Translational Medicine.
This pioneering organ chip advancement signals a promising future where personalized medicine can swiftly and reliably optimize treatment decisions for esophageal adenocarcinoma patients, marking a critical step forward in the fight against one of the world’s deadliest cancers.
