SURGERY Testing the whole tumour – tissue slice assays are an innovative new technology being used to test colorectal cancer drug responses and predict patient responses

In 2018, a new collaboration was formed between Dr Anne Fletcher (Stromal Laboratory, Biomedicine Discovery Institute, Monash University), and Professor Paul McMurrick and Dr Simon Wilkins from the Cabrini Monash University Department of Surgery. The collaboration aims to develop an animal-free platform for testing new cancer drugs in colorectal cancer.

We found that current animal and in vitro human models, while important, didn’t fully capture the complexity of the human tumour and, because of this, results that appeared to work in these models often didn’t translate to patient responses.

While mouse tumours develop in a few weeks, human tumours often take years to develop and, unlike experiments performed in vitro, tumours contain not just the cancerous cells, but also many immune cells, structural cells, scarring proteins and blood vessels. All of these things impact whether or not a new drug will have an effect in patients. The structural cells and scar tissue are particularly important and they are not currently reflected in any commonly used testing model. The newest research shows that these tissues often impair the response to chemotherapy and new immunotherapies, yet, they are not present in our testing platforms.

We decided that if we wanted to know how a tumour responded to a drug, we needed to test the whole tumour, not just the cancer cells.

We have developed an innovative new assay that uses tissue slices from colorectal cancer tumours to accomplish this. Our new testing platform involves a strong partnership between surgeons at Cabrini and scientists at Monash Biomedicine Discovery Institute. If a patient agrees to donate parts of the tumour that would otherwise be thrown out after surgery, our scientists are notified and go and collect it immediately, whether the surgery is at 9am Monday or on a Saturday night. The specimen is chilled, and we use specialised techniques to cut slices of the tumour and culture it in a way that keeps the cells inside alive for up to four days. We then test the response of the whole tumour to drugs, not just the cancer cells but the whole tumour, working together as it works in the body.

So far, we have identified a new lead target that appears to make immunotherapy work better and for more patients. We hope to test this result in a clinical trial within two years.

For the next stage of our research, we are looking for funding to explore whether or not a tumour’s response to chemotherapy agents in our testing platform can predict a patient’s response. This could be game-changing. If successful, we hope it will reduce the need for lengthy chemotherapy trials, where patients wait weeks to see if their tumour responds. Instead, we hope to be able to apply the drugs directly to tumour slices and have an indication of response or resistance within days. With support, we should be able to answer this important question within two years.

This work has been supported by two Cabrini Foundation grants and an anonymous donation to pay for vital equipment for the project.