June 11, 2015
As scientists learn more about the complexity of cancer, the need for personalized treatments based on the patient’s individual cancer has become increasingly pressing.
A new three-dimensional cell culture technology shows promise to develop these precision treatments more quickly and effectively without using animals.
A team of scientists have developed 3D cell cultures, or “organoids” made up of tumor cells from patients with colorectal cancer. The organoids accurately mimic many of the intrinsic properties of the original tumors, such as precise genetic changes. They also enable high-throughput drug screening, which uses computer and robotic automation to evaluate the effectiveness of large numbers of drugs in a short time period.
Mathew Garnett, senior author of the study and a geneticist at Wellcome Trust Sanger Institute in the UK describes how "This is the first time that a collection of cancer organoids, or a living biobank, has been derived from patient tumors.”
3-D organoid cultures derived from healthy and tumor tissue from colorectal cancer patients
are used for a high throughput drug screen to identify genedrug associations
that may facilitate personalized therapy. (Photo courtesy of van de Wetering et al./Cell 2015)
The researchers obtained tumor tissue from 20 patients to develop 22 organoids for investigation. DNA sequencing of the organoids showed that they expressed mutations that were highly similar to the biopsies obtained from the tumors, confirming that the organoids provided accurate models of the original tumors.
Other studies have tried to accomplish the same thing by growing tumors in mice. Many attempts are currently underway to create “mouse-avatars” by transplanting tumor tissue into immune-suppressed mice in the hopes of modeling a particular patient’s cancer. The mice are immune-suppressed to prevent their bodies from rejecting the grafted tissue.
But the mouse-avatars are slow to develop, consuming many months out of a gravely ill patient’s time, sometimes delaying treatment by failing to develop before the patient dies. In about 30% of cases, the engraftment process fails entirely and the mouse tumor never takes hold. The lengthy time span, failure rate and high cost – $10,000 to $12,000 not covered by insurance – place a steep burden on patients already struggling with their disease.
In contrast to tumor implants in mice, organoids offer a number of advantages. Hans Clevers, co-author of the organoid study at the Hubrecht Institute in the Netherlands, explained to Nature how organoids can be developed over several weeks to test drugs very quickly. Further, organoids can be developed for almost all patient tumors. With their compatibility for high-throughput screening, it’s possible to use organoids to test vast numbers of drugs or drug combinations in a relatively short period of time.
Clinical trials using organoids are underway in the Netherlands. Dr. Clevers’ research team is also looking for ways to improve the organoids, such as introducing an immune component to investigate immunotherapy, a very promising area in cancer treatment. This is not possible in a mouse with a compromised immune system.
Three-dimensional organoids show promise for an exciting new avenue of personalizing cancer patient care – one that doesn’t use animals, offers lower cost, greater accuracy and wider accessibility to patients.