We know that approximately 25% of all cancers, including stomach, lung, prostate, colon and liver are caused by infection or inflammation. A strong link has been established between stomach cancer and chronic gastric inflammation but we still don't know why this inflammation triggers cancer in some people but not others.
Our laboratory has discovered that a gene called TLR2 is over-active in approximately 40% of human gastric cancer cases. This gene plays a key role in the immune system, and we have shown that its over-activation promotes the growth and survival of gastric cancer cells.
The aim of this project is to understand exactly how the TLR2 protein promotes the uncontrolled growth of gastric cancer cells, with the hope it will lead to better early detection and/or new therapeutic targets.
What is the need?
Stomach cancer is the third most common cause of cancer-related deaths worldwide. It has a poor overall five-year survival rate of less than 25% due to late detection and limited treatment options.
Surgery alone can only cure a small proportion of patients with locally-invasive advanced stomach cancer, and while chemotherapy can reduce tumour sizes and improve survival compared to surgery-only patients, these rates remain unacceptably low.
There is an urgent need to identify new molecular targets to serve as biomarkers for early detection and/or treatment strategies to improve patient outcomes. These needs are further emphasised by the disappointing results of worldwide clinical trials which have been investigating the safety and efficacy of new drug. Future trials need to be more focused on new personalised therapy.
What impact will this research have?
Overall, the role of the immune system in stomach cancer is ill-defined, and our research addresses this major knowledge gap by uncovering TLR2 as a key driver of stomach cancer.
This finding sets the stage for the potential for TLR2 inhibitors to be included as part of personalised treatment regimes in the future.
The fact inhibitors of TLR2 exist and are currently in early phase testing will pave the way for cost-effective pre-clinical and clincial testing of their efficacy in stomach cancer patients.
Our human studies have also provided preclinical evidence of the use of TLR2 blockade (as a potential new therapeutic strategy) in the clinic for stomach cancer patients. this could now set the stage for translation into clincial practice by establishing a multi-country early phase clinical trials.
"There is an urgent need to identify new targets for early detection and personalised therapies and we believe our research will directly address this."