A world-first clinical trial launched in Melbourne aims to revolutionize treatment for bowel cancer patients by accurately predicting drug responses before therapy begins. The FORECAST-2 trial, based on breakthrough research from the Walter and Eliza Hall Institute (WEHI), could transform the current trial-and-error approach to chemotherapy selection into a personalized treatment strategy.
Bowel cancer, also known as colorectal cancer, claims more than 5,000 Australian lives annually, making it the nation's second deadliest cancer. While early detection enables successful treatment in 99% of cases, less than half of patients are diagnosed at initial stages due to limited symptoms.
Predicting Treatment Response with Mini-Tumors
The innovative approach uses tumor organoids—miniature 3D cancer models grown in the laboratory from a patient's own tissue samples. These grain-of-sand-sized organoids mimic the characteristics of the original cancer, including drug sensitivity.
"Each time you give a patient an ineffective treatment, you lose up to three months on a treatment that won't work," explained Professor Peter Gibbs, Head of Clinical Discovery and Translation at WEHI and medical oncologist at Western Hospital. "Unfortunately, up to 40% of bowel cancer patients will develop advanced stages of the disease, requiring chemotherapy treatment."
The trial addresses a critical challenge in cancer care: currently, there is no reliable way to predict how individual patients will respond to specific chemotherapy drugs, leading some to receive ineffective treatments that delay appropriate care.
Proven Accuracy in Preliminary Research
FORECAST-2 builds on landmark WEHI-led research that validated organoid drug testing as an accurate tool for treatment selection. In the preliminary study, researchers pre-tested chemotherapy drugs on organoids from 30 patients with advanced bowel cancer and found remarkable predictive accuracy:
- 90% accuracy in identifying treatments that would not work for individual patients
- 83% accuracy in predicting treatments that would be effective
Researchers were even able to identify novel treatment combinations for two patients after their organoids showed positive responses to chemotherapy drugs not typically used for bowel cancer.
"Our research to date shows that if a drug has no effect on the organoid, then this treatment would also have no effect on the patient," Professor Gibbs noted. "Knowing what is most likely to work before patients start treatment would make a significant difference to their survival outcome and quality of life."
Expanding Trial Sites and Personalized Medicine
The trial is currently open at Western Health and Melbourne Private Hospital, with plans to expand to five additional sites in the coming months, including Peter MacCallum Cancer Centre, Eastern Health, Northern Health, Royal Melbourne Hospital, and Western Private.
Each patient tissue sample can generate up to eight tumor organoids, allowing researchers to test multiple drug combinations to determine optimal treatment protocols.
Associate Professor Oliver Sieber, a corresponding author on the original study and WEHI Laboratory Head, emphasized the potential impact: "Every cancer is unique and requires a tailored treatment approach for the best outcome. Being able to predict the treatment outcomes for newly diagnosed patients will give us the best chance of identifying the most promising treatments early."
Collaborative Funding and Support
The FORECAST-2 trial is funded by Cancer Australia, with additional research support from multiple organizations including the Stafford Fox Medical Research Foundation, the Australasian Gastro-Intestinal Trials Group (AGITG), Beijing Genomics Institute, The Victorian Cancer Biobank through Cancer Council Victoria, the Victorian State Government, the Guangdong Provincial Key Laboratory of Human Disease Genomics, and the China National GeneBank.
Patients meeting entry criteria may be offered participation in the trial by their treating practitioners at participating hospitals across Australia.
"It's an incredibly exciting moment to see our results be translated into a clinical trial that we hope will become a game-changer for bowel cancer patients in Australia and around the world," concluded Associate Professor Sieber.
