Cold Spring Harbor Validates Organoid Utility in Pancreatic Cancer Treatment

Researchers at New York’s Cold Spring Harbor Laboratory (CSHL) have detailed in the journal Annals of Surgery how pancreatic tumor organoids can help guide decisions about a patient’s initial treatment before tumor-removal surgery. As part of the work, they piloted a rapid organoid screening test that can yield results in as early as a week.

Getting quick results is important because pancreatic cancer patients usually do best if they undergo chemotherapy to shrink their tumor prior to surgery, says Lyudmyla Demyan, a lead author of the study. Demyan is a research fellow in Tuveson’s lab and a surgeon at Northwell Health. If the first round of chemotherapy is not effective, the patient may be switched to a different regimen. But, Demyan says, “you’ve already lost that critical window of opportunity to treat cancer. You’re kind of losing grip on it—it’s spreading very quickly.”

Organoids are tiny 3D clusters of cells that are miniature versions of patients’ tumors. CSHL runs one of the largest cancer organoid facilities in the country, working on a wide range of cancers.

The new study is part of an effort to expand organoids’ role in improving clinical care. “Organoids enable us to recreate and recapitulate each patient's tumor,” says Amber Habowski, a postdoctoral fellow in the Tuveson lab and another lead author of the study. “We then have a model system for each individual patient that we can test drugs on. The idea behind personalized medicine is that if the organoid responds really well, we can maybe predict the patient would also.”

In the study, 136 samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, gender, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, patient-derived organoid (PDO) generation was successful in 71% (15 out of 21) of patients who had received neoadjuvant (NAT) chemotherapy prior to sample collection and in 76% (39 out of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. “We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection,” according to the study.

CSHL is leading a clinical trial called Pancreatic Adenocarcinoma Signature Stratification for Treatment (PASS-01). It is evaluating personalized therapy based on how individual patients’ organoids respond to different chemotherapy treatments. The new pilot test may further optimize personalized chemotherapy treatments.

Demyan hopes she will be able to use the test one day soon to help her patients.