2024 New Treatment Grant - Brooke Pereira

Project Summary

Most pancreatic tumours harbour a mutation in the KRAS gene, which has been historically challenging to target with drugs. Now, Mirati Therapeutics (recently acquired by Bristol Myers Squibb) has made a breakthrough with MRTX1133, a potent drug that inhibits the most common KRAS mutation found in pancreatic cancer (KRAS G12D). This inhibitor has shown much promise in pre-clinical trials, significantly hindering tumour growth. Despite this progress, the adaptability of pancreatic cancer means that after some time the treatment stops working as well. To combat this, we are exploring the use of LSKL, a drug that inhibits thrombospondin-1 (THBS-1), thereby reducing fibrosis. This is important as pancreatic cancers are highly fibrotic, which can prevent effective treatment delivery. By employing cutting-edge imaging at the Garvan Institute, we aim to track the effectiveness of combining MRTX1133 and LSKL within live tumours. This innovative approach could revolutionise the treatment of pancreatic cancer by improving the efficacy of MRTX1133, offering new hope in the fight against this deadly disease. Overall, this research will determine if THBS-1 inhibition can enhance the performance of KRAS inhibitors, potentially leading to more effective therapeutic strategies.