Personalized Approaches for Modeling and Treating Pancreatic Cancer

Pancreatic Cancer Cell

The Cancer Center at BIDMC is now developing technology to maintain live pancreatic tumor cells in culture as 3-D organoids, effectively creating a "living biopsy" of patients' tumors and a potential early advantage against pancreatic cancer.

Led by Senthil Muthuswamy, PhD, Director of the Cell Biology Program in the Cancer Research Institute at BIDMC, this novel method of growing tumor organoids faithfully recreates the tissue organization, differentiation status and other phenotypic traits found in the patient's own malignancy, creating a tumor "avatar" in culture.

Unique Advantages of 3-D Organoids

Human cancer cell lines are typically maintained in two-dimensional monolayer culture for many years, and do not recreate the complex tissue organization used as a defining trait in patient tumors. Tumor organoids, however, exhibit the same 3-D architecture and multilineage differentiation, thereby providing the opportunity to use the organoid cultures to identify personalized treatment strategies, one patient at a time.

Organoid Illustrations

Following biopsy or surgery, a small portion of a tumor (in excess of the need for diagnostic pathology) is sent to the lab; the tissue is digested and cancer cells plated on a dish coated with a soft cushion of proteins. A "cocktail" of growth factors is next introduced to the sample, which then sits for two to three weeks, allowing the cancer cells to form into ball-like structures of varying shapes and sizes.

These 3-D structures are then re-plated and expand the initial growth, several times over. The samples are divided to test targeted precision therapies, which identify the drugs that are most effective in controlling growth of the organoids. The results can then be used to design a therapeutic plan for each patient.

Future Directions

BIDMC's organoid approach gives researchers a "living" biobank of tissue for discovery and validation of new drugs and targets as well as modeling resistance to therapy. Using a cohort of patient samples from which screening can be done for drugs and mutations begins to offer an understanding as to why some patients respond to a particular treatment while others do not.

The short turnaround time for growing organoids and the manageable cost per patient mean that someday soon, they may provide an unprecedented opportunity to practice personalized therapy for patients with pancreatic cancer. Organoids are a promising new strategy in our fight against this formidable disease.

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