Researchers have grown tumours in the lab to accurately predict what drugs will work for people with bowel cancer – before they begin treatment.
The world-first study led by WEHI found drug testing on tumour organoids – 3D cancer models grown from a patient's own tissue – could show how they will respond to a specific cancer treatment.
A clinical trial is now being developed based on the results, which will be the first to validate organoid drug testing as an accurate way to guide treatment selection for people living with bowel cancer – the second-deadliest cancer in Australia.
At a glance
- WEHI-led study proves organoid drug testing can predict how patients with advanced bowel cancer will respond to treatment with 83% accuracy.
- The study is the first in the world to use patient-derived tumour organoids to pre-test the effectiveness of available treatment options and identify potential new therapies for bowel cancer patients.
- A clinical trial based on the findings will launch this year, to assess whether organoid drug testing can revolutionise the way people living with cancer are treated.
Bowel cancer, also known as colorectal cancer, remains the second leading cause of cancer-related deaths worldwide. It is also the fourth most diagnosed cancer in Australia.
While bowel cancer cases can be treated successfully if found early, less than half of all patients are diagnosed at the initial stages due to a lack of symptoms. This means that patients are often diagnosed once the cancer has spread to other parts of the body.
Despite an increasing number of treatment options available to treat bowel cancer, there currently is a limited ability to predict which therapy will be most effective for each patient.
A tumour organoid is a miniature 3D model of a cancer that is the size of a grain of sand. Grown in a laboratory from a patient's own tissue sample, tumour organoids mimic the characteristics of the cancer from which they were created, including sensitivity to drug treatment.
In a landmark study published in Cell Reports Medicine, WEHI researchers showed the technology can identify the most effective treatment for individual bowel cancer patients, by assessing how their organoids responded to specific drugs.
Co-lead researcher and medical oncologist, Professor Peter Gibbs, said the finding could end the current trial-and-error process that goes into selecting a cancer treatment for patients and improve their quality of life.
"Each time you give a patient an ineffective treatment, you lose 2-3 months on something that won't work," Prof Gibbs, also a WEHI Laboratory Head, said.
The window for successful treatment is often limited, so it is vital that we choose the options with the highest chance of success and avoid other treatments that are unlikely to work."
"Our findings show that organoid drug testing is a potential game-changer for cancer treatment, suggesting the possibility of revolutionising personalised medicine and clinician-patient care through improved treatment selection."
As hundreds of organoids can be grown from one patient tissue sample, it is possible to test a wide range of different therapy options in the laboratory.
"Many patients with advanced bowel cancer only get one or two chances at treatment. Knowing what is most likely to work before they start treatment would make a significant difference to their survival outcomes and quality of life," Prof Gibbs said.
Technology of the future
As part of the study the organoids of 30 patients with advanced stages of bowel cancer were used to pre-test chemotherapy drugs in a clinical feasibility trial.
Associate Professor Oliver Sieber, the corresponding author and WEHI Laboratory Head, said seeing the promising results of the study was a groundbreaking moment for the team that validated over 5 years of research.
"If a drug had no effect on the tumour organoid, then this treatment would also have no effect on the patient – and vice versa," Assoc Prof Sieber said.
"Our study showed organoid drug testing was able to predict treatment responses for study patients with a notable 83% accuracy.
"Importantly, pre-testing showed the therapies that won't work with over 90% accuracy."
Researchers also used the organoids to test the effectiveness of chemotherapy drugs that are not commonly used for bowel cancer patients.
They found two patient organoids were sensitive to a drug that is often used for breast and bladder cancers.
"Not only did we show that organoid drug testing could, for the first time, predict patient responses to bowel cancer treatment, we also managed to find a new therapeutic option for patients in our trial.
"That is the power of this incredible technology."
Collaborative trial
The study, with first author Dr Tao Tan, is being translated into a clinical trial that will open at multiple Victorian hospitals this year.
It will be funded by Cancer Australia and the Stafford Fox Medical Research Foundation, with researchers hoping to recruit patients recently diagnosed with bowel cancer to assess whether their tumour organoids can accurately predict individual responses to treatment.
The study, 'Unified framework for patient-derived tumour organoid-based predictive testing of standard-of-care therapies in metastatic colorectal cancer', is published in Cell Reports Medicine (DOI: 10.1016/j.xcrm.2023.101335).
This research was supported by the Australasian Gastro-Intestinal Trials Group (AGITG), the Stafford Fox Medical Research Foundation, Cancer Australia, Beijing Genomics Institute, The Victorian Cancer Biobank through the Cancer Council Victoria and the Victorian Government.
WEHI authors: Tao Tan, Dmitri Mouradov, Margaret Lee, Grace Gard, Yumiko Hirokawa, Shan Li, Michelle Palmieri, Evelyn Leong, Jordan Clarke, Anuratha Sakthianandeswaren, Helen Brasier, Jeanne Tie, Azim Jalali, Antony Burgess, Peter Gibbs and Oliver Sieber.
Image Captions
Tumour Organoid Structure
Pictured: A 3D structure of an organoid formed from human bowel cancer cells. Blue marks the nucleus of the individual cell, green is a protein that sticks each cell together and red shows the cancer cells' orientation.
Credit: WEHI
WEHI Researchers
L-R: Professor Peter Gibbs, Associate Professor Oliver Sieber and Dr Tao Tan.
Credit: WEHI
Organoid Tray
A researcher holding a tray containing lab-grown organoids, which are the size of a grain of sand. Credit: WEHI
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About WEHI (Walter and Eliza Hall Institute of Medical Research)
WEHI is where the world's brightest minds collaborate and innovate to make life-changing scientific discoveries that help people live healthier for longer. Our medical researchers have been serving the community for more than 100 years, making transformative discoveries in cancers, infectious and immune diseases, developmental disorders, and healthy ageing. WEHI brings together diverse and creative people with different experience and expertise to solve some of the world's most complex health problems. With partners across science, health, government, industry, and philanthropy, we are committed to long-term discovery, collaboration, and translation. At WEHI, we are brighter together.
