Cancer |
The critical role of the tumour microenvironment in cancer growth and survival suggests it is vulnerable to intervention.
We aim to improve the survival rate of cancer patients by deciphering and therapeutically exploiting elements of the tumour microenvironment that facilitate chemoresistance.
We achieve this by characterizing the interactions in the tumour microenvironments. This includes investigating the role of cancer associated fibroblasts (CAFs), immune cells, extracellular vesicles (EVs) and the extracellular matrix in facilitating tumour progression.
Using these insights, we then aim to ‘re-shape’ the tumour microenvironment by modulating these pathways, effectively re-sensitising the tumour to chemotherapy and improving treatment efficacy.
Current projects
Our current projects include examining the role of the metastasis suppressor protein NDRG1 in the cross-talk between cancer cells, cancer associated fibroblasts and macrophages.
We are also exploring the roles of vitamins D and E on metabolic cross-talk between breast cancer cells and the tumour microenvironment.
Finally, we are investigating novel targetable mechanisms of metabolic cross-talk between pancreatic cancer cells and fibroblasts to improve response to current chemotherapy.
Highlighted publications
- B Geleta, FS Tout, SC Lim, S Sahni, PJ Jansson, MV Apte, DR Richardson, and Z Kovacevic (2022) Targeting Wnt/Tenascin C-Mediated Cross-Talk between Pancreatic Cancer Cells and Stellate Cells via activation of the Metastasis Suppressor, NDRG1. JBC 298(3):101608. https://pubmed.ncbi.nlm.nih.gov/35065073/
- B Geleta, KC Park, PJ Jansson, S Sahni, S Maleki, Z Xu, T Murakami, M Pajic, MV Apte, DR Richardson and Z Kovacevic (2021) Breaking the cycle: Targeting NDRG1 to inhibit bi-directional oncogenic cross-talk between pancreatic cancer and stroma. FASEBJ 35(2):e21347. https://pubmed.ncbi.nlm.nih.gov/33484481/
- SC Lim, PJ Jansson, S Assinder, S Maleki, DR Richardson and Z Kovacevic (2020) Unique targeting of androgen-dependent and independent AR signaling in prostate cancer to overcome androgen resistance. FASEBJ34(9):1151111528. https://pubmed.ncbi.nlm.nih.gov/32713076/
- 1. Sundus N. Maqbool, Syer C. Lim, Rumeza Hanif, Des R. Richardson, Patric J. Jansson and Zaklina Kovacevic (2020) Overcoming tamoxifen resistance in estrogen receptor positive breast cancer using a novel class of thiosemicarbazone anti-cancer agents. British J. Pharmacology 177(10):2365-2380. https://pubmed.ncbi.nlm.nih.gov/31975484/
- FS Tout, HH Milioli, S Roslan, PJ Jansson, M Dharmasivam, D Graham, R Anderson, T Wijesinghe, M Gholam Azad, DR Richardson, Z Kovacevic (2023) An Innovative Non-Hormonal Strategy Targeting Redox Active Metals to Down-Regulate Estrogen-, Progesterone-, Androgen- and Prolactin-Receptors in Breast Cancer. Pharmacol. Res. 193:106806. https://pubmed.ncbi.nlm.nih.gov/37244387/
Our experts
Dr. Zaklina Kovacevic - Group Leader
Dr. Kovacevic completed her PhD in 2011 at the University of Sydney, where she also undertook her post-doctoral studies, being supported by joint NHMRC and CINSW Early Career and Career Development Fellowships. Her PhD studies focused on developing a new class of metal-binding thiosemicarbazones as anti-cancer agents and elucidating their molecular mechanisms in numerous cancer types including pancreatic, prostate and breast cancers.
In 2020 Dr. Kovacevic established her independent research group at the University of Sydney, and in 2023 she relocated to UNSW where she now heads the Tumour Microenvironment group within the School of Biomedical Sciences. Her research is focused on understanding the cross-talk between cancer cells and the tumour microenvironment, with a particular interest in pancreatic cancer.
She has published 81 research outputs (>6500 citations) and attracted >$8.5 million in research grants/fellowships ($3 million as lead investigator). Her research achievements were recognized by the 2016 Premier's Award for Outstanding Cancer Research Fellow of the Year and the 2016 Sydney Medical School Award for Excellence for Outstanding Early Career Researcher.
Team members
- Dr. Saranya Pounraj – post-doctoral fellow
- Mr. Jiawei Chang (Kevin) – PhD student
- Mr. Shafi Alenizi – PhD student
- Miss. Yujie Li – PhD student
- Mr. Mekonnen Sisay – PhD student
- Miss. Balquees Kanwal – visiting PhD student
Research Theme