Colorectal cancer (CRC) is still the second leading cause of cancer death in Australia, and research into its causes and mechanisms is urgently needed.

In a significant development in Cabrini’s continued work against colorectal cancer (CRC), Associate Professor Anne Fletcher PhD from Monash University’s Biomedicine Discovery Institute and Dr. Simon Wilkins, PhD, Senior Research Fellow at Cabrini Monash University Department of Surgery (CMUDS), have been awarded a prestigious National Health and Medical Research Council of Australia (NHMRC) Ideas Grant securing a substantial $1,350,991 over five years.

Their groundbreaking project, titled “COX2 driven T cell suppression in the colorectal cancer microenvironment”, is set to propel the boundaries of innovation in cancer research. The grant combines cutting-edge translational research techniques, showcasing Cabrini Hospital and Monash University’s commitment to advancing colorectal cancer research and marking an important step in the ongoing fight against colorectal cancer.

The research team on the grant also includes investigators Prof. Paul McMurrick (CMUDS), Prof. Helen Abud (Monash Biomedicine Discovery Institute), Prof. Roger Daly (Monash Uni), Dr. Christian Nefzger (Uni QLD), Dr. Christine Georges (CMUDS) and Prof. Mohammad Asghari-Jafarabadi (Cabrini Research).

Attributing Quotes:
Quoting Professor Paul McMurrick (Head of Cabrini Monash University Department of Surgery)
“The success of this grant reflects the importance of the close scientific and clinical collaboration between Cabrini Monash Department of Surgery and our partners in the Biodiscovery Institute at Monash.”

Quoting Associate Professor Anne Fletcher (Monash University, Biomedicine Discovery Institute)
“Bowel cancer is a terrible disease. It’s the second deadliest cancer in Australia. For some cancers, new immune-targeting drugs called checkpoint inhibitors have been effective, but in bowel cancer, only 5% of patients can take them. We’re targeting some cells called fibroblasts, which act like the soil that cancer grows in. We’ve found that those fibroblasts switch off immune cells, and we’re now testing ways to block those fibroblasts so that immunotherapies can work for more patients.”

For media inquiries, please contact: Jodie Mills, Cabrini Communications and Media Lead, ph 0436 928 801 or jmills@cabrini.com.au

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Additional information:
The research embarks on a pioneering exploration into the role of COX2 inhibitors in overcoming immune suppression caused by Cancer-Associated Fibroblasts (CAFs) in colorectal cancer. This revolutionary breakthrough has the potential to transform the landscape of treatment for the majority (95%) of patients currently left without viable options, for whom checkpoint inhibitors are currently ineffective.

The research project is affiliated with Let’s Beat Bowel Cancer (LBBC), a consumer education and fundraising group established by CMUDS. LBBC has been actively disseminating information on bowel cancer for approximately 16 years through various channels, including its website, patient education campaigns, community meetings, and social media platforms.

The NHMRC Ideas grant paves the way for new discoveries and acts as a springboard for essential preliminary work leading to a clinical trial. Identifying patient subgroups, deciphering drug interactions, and understanding T cell responses are pivotal milestones moving us closer to a future where immunotherapy can triumph over colorectal cancer.

This NHMRC Ideas grant builds upon the success of Cabrini Foundation grants awarded to the research team in 2019 and 2021, underscoring the profound impact of incremental progress in driving colossal advancements in colorectal cancer research.

Key Details:

• Title: COX2 driven T cell suppression in the colorectal cancer microenvironment
• Duration: 5 years
• Amount: $1,350,991
• Funder: NHMRC Ideas grant scheme

Project Overview: Title: COX2 driven T cell suppression in the colorectal cancer microenvironment Duration: 5 years Amount: $1,350,991 Funder: National Health and Medical Research Council of Australia, Ideas grant scheme.

Research Team: Chief Investigators: A/Prof. Anne Fletcher (Monash University, Biomedicine Discovery Institute) and Dr. Simon Wilkins (Cabrini Monash University Department of Surgery)
Associate Investigators: Prof. Paul McMurrick (Cabrini Monash University Dept of Surgery), Prof. Helen Abud (Monash Biomedicine Discovery Institute), Prof. Roger Daly (Monash Uni), Dr. Christian Nefzger (Uni QLD), Dr. Christine Georges (Cabrini Monash University Dept of Surgery), and Prof. Mohammad Asghari-Jafarabadi (Cabrini Research).

Consumer Education and Engagement Partners: The research project is affiliated with Let’s Beat Bowel Cancer (LBBC), and as such, LBBC will play a crucial role in providing ongoing feedback, raising awareness, and ensuring effective communication of the research outcomes to the public.

Media Summary: Colorectal cancer (CRC) remains the second leading cause of cancer death in Australia. Despite the success of checkpoint inhibitors in many cancers, they are ineffective for over 95% of colorectal cancer patients. The research project aims to explore the potential of COX2 inhibitors in making checkpoint inhibitor drugs more effective by targeting cancer-associated fibroblasts (CAFs) within the colorectal cancer microenvironment.

Plain Language Summary: The research focuses on understanding why checkpoint inhibitors, a promising class of cancer therapies, are ineffective for most colorectal cancer patients. The team discovered that the immune response is hindered by structural tumour cells called Cancer-Associated Fibroblasts (CAFs). These CAFs use a molecule called COX2 to suppress T cell activation. The researchers propose using COX2 inhibitors, already widely used and with a strong safety profile, to interrupt this suppression, potentially making checkpoint inhibitors more effective.

Clinical Trial Proposal: The team will use the grant to conduct essential preliminary work for a clinical trial, including identifying patient subgroups for testing, understanding how COX2 and immunotherapy drugs interact, and determining which types of T cells respond. The study aims to pave the way for a groundbreaking clinical trial testing the efficacy of COX2-targeting drugs in improving immunotherapy outcomes for colorectal cancer patients.

Cabrini Foundation Support: This NHMRC Ideas grant builds on the success of two Cabrini Foundation grants awarded in 2019 and 2021, showcasing the impact of smaller research grants in catalysing significant advancements in colorectal cancer research.

Research Innovation: The grant brings together cutting-edge translational research techniques, including organoids and transcriptomics, the tissue microarray, and the Cabrini Monash Colorectal Neoplasia Database, marking a significant step in the ongoing fight against colorectal cancer.

About the National Health and Medical Research Council of Australia (NHMRC) Ideas Grant
The objective of the Ideas Grant scheme is to support innovative research projects addressing a specific question(s).

The expected outcomes are:
– innovative and creative research
– funding of researchers at all career stages
– funding any area of health and medical research from discovery to implementation.

The scheme provides particular opportunities for early- and mid-career researchers.