Advancing targeted therapies for metastatic breast and gynaecologic cancers using RNA-based therapeutics with lipid nanoparticle (LNP) delivery system
Our lab is funded by the national breast cancer foundation (NCBF) and the department of defence of the United States of America (DoD). This funded project is suitable for Honours/Master and PhD as well as clinical students’ project that can be scoped as smaller or larger projects depending on the HDR degree/ interest of the student.
Background
Cancer ranks as the second leading cause of death globally and Breast cancer (BC) stands as the most prevalent malignancy among women. Despite advancements in early diagnosis and personalised treatment approaches for cancer, recurrence and metastasis remain the leading causes of cancer-related mortality (~90%). Conventional chemotherapy yields limited efficacy for metastatic disease and recurrent metastatic breast cancer as well as gynecologic cancers, such as ovarian and endometrial cancer, where the 5-year survival rate remains below 20%. Our research has demonstrated that genetic inhibition of Cep55 reduces cancer progression and metastatic potential in mouse models. However, Cep55 is considered undruggable due to its coiled-coil structure. Therefore, we propose an innovative approach using antisense oligonucleotides (ASOs) to inhibit Cep55 expression at the mRNA level. This strategy aims to provide proof-of-concept for targeting undruggable and hard-to-treat cancers, particularly invasive, aggressive, and advanced cancers, as well as metastasis, through preclinical studies both in vitro and in vivo.
Aims
- Screening ASOs and performing functional assays across a spectrum of human and mouse metastatic breast, ovarian and endometrial cancer cell lines, tumouroids, patient-derived xenograft organoids (PDXOs), and patient-derived organoids (PDOs).
- Evaluating preclinically whether ASO-Lipid nanoparticles (LNP) impedes cancer growth, progression, and spread and examining the efficacy, stability, specificity, and toxicity in-vivo.
Investigating the mechanism of action and functional role of drug in tumour-microenvironment and metastasis by spatial transcriptomics.