Patient Models as Tumour Avatar Fights Off Colorectal Cancer

Using miniature reproductions of organs and tissues derived from patients to expose new treatments in colorectal cancer, paves way for customized therapies.

A new approach to facilitate personalized treatment of Colorectal cancer by using a new platform that combines statistical modeling and patient-derived organoids has been demonstrated in the Journal of Experimental & Clinical Cancer Research.

Understanding Colorectal Cancer Treatment

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide with an incidence exceeding a million newly diagnosed cases per year. It originates from uncontrolled cellular growth in the epithelial layer of the colon.

These lesions begin with hyperplasia, and before becoming malignant they are known as polyps and can be removed during regular colonoscopy (local excision). However, if untreated, adenomatous polyps can become dysplastic and further develop into a carcinoma.

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‘A new approach for designing personalized treatment for colorectal cancer (CRC) patients tests organoid efficacy with mathematical modeling.’

Its treatment is based primarily on a combination of chemotherapies called FOLFOXIRI. However, its effectiveness varies from patient to patient and its side effects are significant. It also leads to progressive drug resistance in most patients.

A research team has found the solution to optimized chemotherapy for colorectal cancer patients by using organoids. These three-dimensional cellular structures, created in the laboratory, reproduce the structure and functions of certain tissues and organs.

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They have some important physiological differences, such as not having vascular or nervous systems. However, they are very effective models for testing treatments. Researchers started with cancer tissue taken from untreated patients at the Geneva University Hospitals (HUG).

By cultivating stem cells from these tissues - which gradually divided and organized themselves into three-dimensional structures - the scientists were able to produce organoids, or tumoroids, from each patient’s tumor.

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Then tested different drugs on these models, without knowing their genetic background. This individual background largely determines the effectiveness of the treatments. The researchers, therefore, started from scratch, basing their entire study on the observation of the cells’ response in real-time.

These tumor avatars were exposed to a range of seven treatments currently in clinical use. Depending on the response of each patient organoid, the combination, and dosages of these treatments were adapted.

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All results were mathematically modeled to predict the optimal efficacy and doses for each organoid, i.e. for each patient. These tests were carried out over two weeks. This is a clinically relevant time frame: it is the time frame currently needed by the medical profession to choose a treatment after diagnosis.

This innovative approach, without animal models, has just been patented. It offers personalized treatment for many forms of cancer, but also other diseases such as cardiovascular or viral diseases.

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Trials are underway for renal cancer. For the research team, the next step will be to work on organoids from pre-treated colon cancer tumors, which therefore show signs of resistance. The aim will also be to shorten the duration of the optimization process.

Source-Eurekalert