Congratulations to Professor Brendan Jenkins and his team, who have been awarded $288,536 from Cancer Council Victoria (CCV) to fund research into pancreatic cancer.
Professor Jenkins‘ project was one of 13 projects to receive a share in $3.8 million in 2021 from CCV’s Grants-in-Aid program, which funds high-quality research into the treatment, causes, detection and prevention of all cancers.
The study will investigate a precision medicine approach to a form of pancreatic cancer called pancreatic ductal adenocarcinoma (PDAC). Researchers will examine a receptor in the body’s immune system which could potentially be targeted by therapies to fight tumours, including those that have become resistant to chemotherapy.
Uncovering the broad clinical utility of the innate immune pattern recognition receptor, Toll-like receptor 2, in pancreatic cancer
Professor Brendan Jenkins
Research will address the under appreciated role of innate immunity in pancreatic ductal adenocarcinoma (PDAC) by demonstrating the broad clinical utility of the innate immune receptor, TLR2, as a therapeutic target and biomarker.
Causes: Host factors of the immune system with tumour-promoting activity in the pancreas are ill-defined. Furthermore, the recent emergence that gut-derived microbes can contribute to the pathogenesis of PDAC, as well as chemoresistance, emphasises the critical need to identify molecular regulators of innate immunity (the first line of host defence against microbes) which interact with pathogenic microbes in the pancreas to drive the ensuing immune-related oncogenic responses. In this regard, our compelling preliminary data lead us to propose that the pattern recognition receptor, TLR2, which recognizes a diverse range of host- and microbial-derived ligands, plays a hitherto unknown causal role in the development of PDAC, as well as resistance to chemotherapeutic drugs in PDAC such as gemcitabine/abraxane.
Treatment: Research promises to provide robust preclinical evidence for the efficacy of TLR2 blockade (with a humanised, clinical grade anti-TLR2 monoclonal antibody) as a potential new adjuvant second- and/or third-line therapeutic strategy for PDAC patients resistant to chemotherapy. In this respect, the study will evaluate the tantalising prospect that antibody-mediated anti-TLR2 therapy not only has direct anti-tumorigenic activity, but also can sensitise chemo-resistant patient tumours to gemcitabine/abraxane, with potential utility to other PDAC chemotherapeutics (i.e. FOLFIRINOX).
In terms of translation into clinical practice, our forerunner studies have established a translational pipeline for precision medicine in PDAC which has underpinned the implementation of a phase II PDAC precision medicine clinical trial – a first – using the EGFR inhibitor panitumumab as second-line therapy for KRAS wild-type PDAC (CIB Croagh; Australia New Zealand Clinical Trials Registry, ACTRN12617000540314).
Therefore, we have a clear translational path for our research to accelerate the introduction of antibody-mediated anti-TLR2 therapy as a safe and efficacious novel treatment modality for precision medicine in PDAC. Accordingly, our research presents a timely and exciting opportunity to improve the overall response rates and survival outcomes for PDAC patients.