Organoid research open ups new horizons in mCRC

Professor Peter Gibbs

Professor Peter Gibbs

Patient-derived tumour organoids will serve as a new model in which to identify personalised treatments for patients with advanced bowel cancer, Australian researchers say.

Organoids are tissue cultures grown in vitro from stem cells, which self-organise to replicate aspects of the function and structure of an organ in miniature.

Medical oncologist Professor Peter Gibbs, from the University of Melbourne and Walter and Eliza Hall Institute of Medical Research, has been awarded the GI Cancer Institute’s $200,000 Innovation Fund grant to lead organoid research.

The project will enrol at least 30 patients with metastatic colorectal cancer who have exhausted all other treatment options.

Fresh biopsies of their cancers will be obtained and cultured in the laboratory to establish the organoids. Potential therapies will then be tested in the organoids to indicate how the patients’ tumours might respond to the drugs and hopefully identify the best treatment for each patient.

Professor Gibbs told the limbic the most immediate opportunity was in re-purposing chemotherapy drugs that have some activity in colorectal cancer but have never made it through to major phase 3 studies.

“We know they can work very well in patients, and are trying to identify the subset of patients who respond to chemotherapy drugs that we don’t usually think about for CRC such temozolomide, gemcitabine and pemetrexed.”

“If we can use the organoids to find the 1 in 10 or 1 in 5 patients who will benefit then we can offer these treatments. They are ready to go, they are cheap and available. We could expand our repertoire of treatments for CRC very quickly and the same thing could be done for other tumour types as well.”

He said researchers were aiming to accelerate the process of growing organoids and testing drugs to about four weeks from biopsy to report to clinician.

Like patient-derived xenografts, patient-derived tumour organoids have the characteristics of the original tumour.

However they were faster to return results, avoided the ethical issues around using experimental animals, were cheaper in terms of infrastructure once in place, and can be done on a larger scale.

Professor Gibbs said as part of his research protocol, all the original tumours and organoids will be sequenced to confirm the organoids have the same molecular phenotype as the tumour it was derived from.

Recruitment was due to start in the New Year with results expected in about two years.

He added that organoids would also be useful in new drug development allowing for prescreening of promising drugs before they move forward to clinical trials.

“And once you get to a clinical trial, using organoids to identify which patients are more likely to respond to new investigational drugs.”

He said they would also be useful in the future in answering questions about sequencing and combinations of currently used drugs.

“For example, do you start with FOLFOX or FOLFIRI? At the moment, there is no indicator as to which is the best approach but maybe with the organoids we could look at that.”

Professor Tim Price, Chair of the GI Cancer Institute, said the research was groundbreaking in its contribution towards personalised medicine.

“New research is the only way we are going to see changes in the quality of life and survival rates for bowel cancer patients,” he said.

“By funding this study, we will be able to offer personalised treatment when standard therapies are not working for them.”

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