Garvan scientists were awarded two highly competitive National Health and Medical Research Council Ideas Grants for cutting-edge projects in breast cancer and pancreatic cancer.
The Ideas Grant scheme is a competitive, peer-reviewed grants system that provides up to four years of funding for innovative projects. The successful Garvan researchers will investigate whether targeting the cells forming the environment of tumours, otherwise known as the cancer ‘ecosystem’, could lead to advances in breast and pancreatic cancer treatments and improve outcomes for patients.
Epigenetic therapy for ER+ breast cancer
Dr Joanna Achinger-Kawecka, Leader of the 3D Epigenome in Cancer Group at Garvan, is spearheading new research investigating whether targeting the epigenome – the layer of instructions that organises and regulates DNA’s activity – could re-sensitise treatment-resistant breast cancers.
An estimated 70% of all diagnosed breast cancers are oestrogen receptor positive (ER+), which means their growth is activated by oestrogen. While endocrine therapy that suppresses oestrogen in the body can slow or stop the growth of these tumours, more than 30% of patients develop resistance, with their tumours no longer requiring oestrogen to grow.
Dr Achinger-Kawecka’s previous work revealed that epigenetic therapy has the potential to target endocrine-resistant ER+ breast cancer by reversing changes to the 3D structure of DNA. In this three-year project, she will investigate how the tumour ecosystem, which includes various cell types and molecules surrounding the tumour, impacts the response to epigenetic therapy in endocrine-resistant ER+ breast cancer. Using sophisticated single-cell techniques to study the molecular changes in the breast cancer ecosystem at the cellular level, she aims to identify new therapeutic targets to enhance the effectiveness of epigenetic therapy and improve outcomes for ER+ breast cancer patients with treatment resistance.
Can blocking a key enzyme improve pancreatic cancer treatment?
Dr David Herrmann, Leader of the Cell Dynamics Group at Garvan, will receive funding over three years for his project to test whether blocking a key enzyme involved in the formation of scar tissue around pancreatic tumours can enhance treatment delivery and improve patient survival rates.
Tissue scarring or ‘fibrosis’ poses a major barrier for drug delivery and fuels treatment resistance in aggressive pancreatic cancer. This is because it creates a dense tissue barrier around the tumour that obstructs chemotherapy delivery and compresses blood vessels, reducing oxygen supply.
Using advanced single-cell intravital imaging technology at Garvan’s ACRF INCITe Centre, where individual cells are visualised in real-time in animal models, they will determine the efficacy of blocking the Plod1 enzyme to clear the way for chemotherapy delivery. Findings will then be validated in models grown from tumours donated by patients.
Dr Herrmann’s hope is that with this new approach, they can reduce scar tissue and bring the environment around the tumour back to a more normal state. The research could lead to new combination strategies that make meaningful headway against one of the deadliest forms of cancer.
Dr Joanna Achinger-Kawecka and Dr David Herrmann are Conjoint Lecturers at St Vincent's Clinical School, Faculty of Medicine and Health, UNSW Sydney.