Tailored Colorectal Cancer Treatment With Organoids for Hopeless Cases

As part of the “Mars Bleu” operation, which is dedicated to the early detection of colorectal cancer, researchers from the Gustave Roussy Institute announced the start of a novel clinical trial. It consists in the creation of 3D mini-tumors that will make it possible to test different available treatments in order to know which one should be administered according to the case.

Anal Cancer

Diagram Showing Stage 1 Anal Cancer Courtesy of Wikipedia

Colorectal cancer is the third most common type of cancer and the second most fatal cancer, responsible for over 51,020 deaths per year. In 2018, more than 101,420 people have been diagnosed with colorectal cancer.

It develops on the walls of the colon or rectum from benign tumors called polyps. These polyps, which can occur without symptoms, can develop into cancer in a process that can take up to 10 years. If diagnosed in a localized phase, it can be treated surgically. But if it spreads and forms metastases, it can rarely be cured.

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A new study carried out by researchers from the Gustave Roussy Institute aims to offer patients in this situation a customized treatment with organoids, a 3D copy of their tumors made from a sample. These have the same characteristics of the tissue (healthy or diseased, e.g. tumour) from which they originate. “To this day, chemotherapy is the reference treatment for colorectal cancer and more generally for digestive cancer. These cancers have not benefited from the two most recent therapeutic revolutions in oncology, namely immunotherapy and precision medicine,” explains Dr. David Malka, an oncologist with Gustave Roussy.

With a miniature cancer avatar

He adds: “Some patients quickly find themselves in a therapeutic impasse that is difficult to accept because they are often still able to receive other treatments. “In order to identify additional treatment options for this patient profile, the doctors at the Gustave Roussy Institute developed Organotreat-01, a clinical trial called “personalized medicine” based on organoids. “This miniature cancer avatar reproduces the cancers special features: biological properties, resistance to therapy, a reflection of the patient’s therapeutic history”, says Prof. Fanny Jaulin, who co-directs the Organotreat-01 study.

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The aim of this first study is to use these 3D mini-tumors to determine the best possible treatment from a panel of drugs and then administer it to the patient. “Although organoids are now widely used in basic research, no clinical trial has yet investigated their usefulness in guiding the treatment of patients with digestive cancer,” adds Professor Fanny Jaulin. The first step of the project is to produce in the laboratory the organoids of patients with advanced colorectal, liver, biliary or pancreatic cancer from a tumor that has been non-invasively removed from the patient.

Determine the best treatment in a few weeks

Twenty-six conventional or specific therapeutic chemotherapeutic agents authorized and indicated for the treatment of digestive or other cancers will then be tested on the organoids concerned. The results will be analyzed in order to establish a list of tumor characteristics within three to six weeks after the biopsy. The aim is twofold: to identify possible additional therapeutic options and to administer to the patient as soon as possible the treatment that would have been most effective on the organoids derived from his or her own tumor. This process will also provide a better understanding of why the tumor is resistant or responds to certain treatments.

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The Institute reports that 50 patients will be enrolled in the clinical trial from January 2021 onwards. “However, if we can find additional funding, we hope to expand our drug pipeline to 39 compounds, which would multiply the chances of success and combination options. We also want to understand what genetic abnormalities may be associated with treatment response,” concludes Fanny Jaulin. If the study is conclusive, the researchers hope that this innovative procedure can be extended to all patients for whom oncologists no longer offer standard treatment.



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