Defining The Role Of Reserve Stem Cells In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$563,739.00
Summary
Over 800,000 deaths from stomach cancer occur annually. This often fatal disease is caused by chronic inflammation of the stomach lining. This proposal will investigate how stomach inflammation ‘reprograms’ a new type of 'cancer stem cell' to form tumours and evaluate ways to therapeutically target these cells to prevent disease. Collectively, these studies will inform new approaches for stomach cancer prevention and treatment.
Understanding the mechanisms in the development of mutations in cancers will assist in development of targeted therapies to overcome chemotherapy resistance. The recently discovered TMPRSS2:ERG fusion in prostate cancer is unique as dominant fusion translocations are uncommon in solid organ malignancy. Activation induced cytidine deaminase (AID) is thought to play a role. Understanding the role of AID and downstream DNA repair pathways may be a target for future therapies in cancer.
Fzd receptors are often upregulated in gastric cancer, and recent studies have shown that targeting these receptors has be effective at reducing cancer cell growth in other cancers including prostate and breast. This project will use cutting edge technology to firstly determine the specific requirement for Fzd receptors during gastric cancer and then determine the therapeutic benefit of using an antibody to target these receptors in mouse models and human gastric cancer cells.
Therapeutically Exploiting Non-oncogene Addiction And Defining Genetic Interactions For Disease Progression In A Preclinical Model Of Inflammation-dependent Gastric Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
Cancers of the stomach are often associated with chronic inflammation and represent a major health burden with little treatment options available. We propose to test whether drugs undergoing clinical testing for other diseases may have beneficial effects in a preclinical model of gastric cancer, and establish the genetic interaction required for gastric cancer progression. The study outcomes may highlight novel therapeutic opportunities for the clinic.