Poster Presentation 38th Lorne Cancer Conference 2026

Nuclear-encoded mitochondrial-associated genes as potential therapeutic targets for metastatic prostate cancer (#110)

Jasmine M Bacon 1 , Johanna L Jones 1 , Guei-Sheung Liu 1 2 3 , Joanne L Dickinson 1 , Kelsie Raspin 1
  1. Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
  2. Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia
  3. Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia

Mitochondria are essential for the survival and function of our cells, through facilitating and regulating energy, metabolism, and diverse signalling pathways. Cancer cells are known to undergo metabolic reprogramming, hijacking mitochondrial functions to promote tumour survival and rapid growth. These changes actively promote the metastatic cascade, including the circulation of cancer cells and colonisation of distant sites. Over 90% of cancer-related deaths are due to metastasis1, and in metastatic prostate cancer over 84% of metastatic lesions occur in bone2, 3. Bone metastases are associated with significant mortality and are debilitating and painful, severely impacting a patients’ quality of life. Metastatic prostate cancer is currently incurable due to ineffective and largely palliative treatment options; however, mitochondria present as a novel biomarker and/or therapeutic target for metastatic prostate cancer. Healthy prostate cells rely on altered metabolic pathways compared to other healthy human cells causing prostate cancer to deviate from traditional cancer metabolism models, potentially exposing unique vulnerabilities not seen in other cancer cell types.

We investigated five nuclear-encoded mitochondrial-associated genes as novel therapeutic targets that drive metabolic adaptations enabling prostate cancer cells to metastasise to bone. We analysed publicly available gene expression data, as well as a rare resource of matched patient primary-bone metastasis samples, and assessed associations between gene expression and clinicopathological features, including disease stage, recurrence, and survival. Functional validation was performed in vitro using aggressive prostate cancer cell lines to evaluate the impact of gene modulation on invasion, migration, proliferation, and mitochondrial activity. Additionally, we have employed a zebrafish xenograft model to assess metastatic potential in vivo, enabling real-time analysis of invasion and colonisation.

This research explores novel drivers of metastatic prostate cancer, utilising an innovative in vivo model to evaluate their potential as biomarkers and therapeutic targets of aggressive disease. This research aims to address the limitations of current treatment strategies and pave the way for effective, personalised therapies that could transform the management of metastatic prostate cancer.

  1. Hensel, J. and G.N. Thalmann, Biology of Bone Metastases in Prostate Cancer. Urology, 2016. 92: p. 6-13.
  2. Bubendorf, L., et al., Metastatic patterns of prostate cancer: An autopsy study of 1,589 patients. Human Pathology, 2000. 31(5): p. 578-583.
  3. Gandaglia, G., et al., Distribution of metastatic sites in patients with prostate cancer: A population‐based analysis. The Prostate, 2014. 74(2): p. 210-216.