Cancer treatment is not one size fits all. Physicians must consider the different mutations, tumor formations, and affected tissue types of a case and tailor treatment to each patient. To find the most effective treatment for each patient, doctors and researchers sometimes use patient derived tumor samples to test which drugs work best on a particular tumor before administering the drugs to patients.
However, current patient derived tissue models such as organoids are limited by slow results, low reproducibility, and an inaccurate representation of the tumor environment. In a recent Cell Stem Cell study, researchers at Duke University developed a system for generating patient derived miniature tissue spheres that are smaller than organoids (1). The researchers used these tiny tissue samples, called micro-organospheres (MOS), to assess a broad range of drugs and produce results in as little as two weeks.
The new study represents “a new dimension of the drug discovery field,” said Jesse Boehm, a cancer researcher at the Broad Institute of MIT and Harvard who was not affiliated with this study. “This is a thorough proof-of-concept study that begins to show the feasibility of each step in the process,” from device manufacturing, to confirming the accuracy of the model, and to performing drug studies.
Xiling Shen, a cancer biologist at Duke University and author of the study, used samples from a tumor biopsy to generate micro-tumors ex vivo that represent the genetics and microenvironment of the original tumor. Since MOS are smaller than organoids, they have a shorter growth timeline that allows for faster drug testing. One tumor biopsy can be used to generate more than a thousand MOS, maximizing the use of one sample. The researchers recapitulated the patient’s immune microenvironment by retaining immune cells in the MOS and ensuring that they responded to immunotherapy.
To validate their approach, Shen’s team first tested more than one hundred FDA-approved drugs on MOS derived from a patient with rectal cancer and found that the cancer was sensitive to the drug oxaliplatin. The researchers then incorporated biopsies from 7 additional patients into the sample group. Four samples were sensitive to oxaliplatin, and the other four were resistant.
The team next gave each patient oxaliplatin, and the results matched Shen’s team’s prediction; the four patients whose MOS were sensitive to oxaliplatin responded well to the treatment. The sizes of their liver lesions decreased. Three of the four patients resistant to oxaliplatin did not respond to the drug.
With their MOS system, Shen’s team can screen a wide range of drugs, including checkpoint inhibitors, which are drugs that help cancer cells detect and attack cancerous cells, as well as immune modulators and antibody drugs. Shen’s team started a clinical trial in June of 2022 to test patient tumor samples on a wider scale.
The authors of the study also established their own startup company, Xilis, to develop a MOS commercial assay for use in the clinic. Shen believes that researchers could translate this proof of concept to other diseases and patient derived cell types to study conditions that don’t have reliable drug testing models.
“For the first time, you can reliably do drug testing in a clinic setting within 10 days, and also be able to assess immune drugs that right now don't have comparable preclinical models,” said Shen.
- Ding, S. et al. Patient-derived micro-organospheres enable clinical precision oncology. Cell Stem Cell 29, 905-917 (2022).