Dr Pierre Dilda
Field: Basic Pharmacology
Phone: +61 2 93858796
Fax: +61 2 93851510
Overcoming the acquired or innate chemotherapy resistance of malignant tumours has been an ongoing challenge ever since the development of the first chemotherapeutic agents.
The discovery that arsenic trioxide induces complete remission in a high percentage of patients with acute promyelocytic leukaemia has renewed interest in arsenic for the treatment of cancer. Organic arsenicals are currently being investigated in cancer therapy due to their generally better toxicity profile compared to inorganic derivatives. Dr Dilda has specialised in organic arsenical anti-cancer compounds.
GSAO (4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide), an arsenic-based GSH-conjugate, is a mitochondrial poison that inhibits proliferating, but not growth-quiescent, endothelial cells in vitro and angiogenesis in vivo. It demonstrated anti tumor activity evaluated in clinical. For GSAO, extracellular γGT activity is an essential and limiting step in its activation into membrane permeable compounds. Indeed, it has recently been demonstrated that tumor γGT could be used for therapeutic delivery.
PENAO, (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), a second generation compound, shares the same mitochondrial molecular target as GSAO. PENAO, 20-fold more potent than GSAO, demonstrates both in vitro and in animal models anti-proliferative and anti-angiogenic activities. The combination of these two properties leads to strong anti-tumour activity. Interestingly, PENAO has a strong anti-proliferative activity against glioblastoma cell lines and primary isolates of diffuse intrinsic pontine glioma. In vivo, PENAO demonstrated preclinical activity without signs of toxicity in tumor models of glioblastoma, pancreatic carcinoma and ovarian carcinoma. PENAO is currently tested in clinical Phase I/IIa in patients with solid tumours refractory to standard chemotherapy. Our recent work demonstrated that when combined with other drugs such as mTOR and EGFR inhibitors, PENAO anti-tumour activity is massively enhanced notably on drug resistant tumour cells. This discovery offers valuable options to the clinicians for the design of PENAO clinical Phase II.
We have recently characterised a novel polyarsenic adamantane-type class of compounds. The potency of the novel polyarsenic adamantane-type class of compounds was demonstrated in three types of drug resistant cancers. These compounds, not affected by resistance mechanisms responsible for the failure of cancer chemotherapeutics, are notably a hope for the treatment of cancers with a poor overall survival.
Dr Dilda's research has been published in the top 3 cancer biology journals such as Cancer Cell, Journal of the National Cancer Institute and Cancer Research and was the subject of commentaries in Nature Reviews Cancer and Science-Business eXchange.
PhD (UniParisV, France)
Broad Research Areas:
Pharmacology, Biochemistry, Cancer, Molecular Structure & Drug Design, Metabolism
Specific Research Keywords:
Drug Discovery, Cancer Drug Development and Pharmacology, Drug Resistance, Medicinal Chemistry, Arsenical-based drugs
The Cancer Council NSW. Campfires Against Cancer Research Fellowship 2006-2010. Project title: “New arsenical-based cancer drugs” ($500,000 over 5 years).
- Project Grant
NHMRC Project Grant 2010-2012. Project title: “Investigation of a tumour enzyme as a predictor of patient response to an Australian anti-cancer drug”. I am chief investigator A and am responsible for the preliminary data presented in the application. Dr Hendrik-Tobias Arkenau is CIB. Associate investigators are Prof. M. Apte, Dr. A. de Fazio, Prof. R. Ward, Dr. S. Decollogne and Prof. A. Pompella ($348,750 over 3 years).
- Program Grants
- The Cancer Council NSW. Research Program Grant 2011-2015. Project title: “Metabolism inhibitors for the treatment of brain and pancreatic cancer”. Chief investigators Prof. Philip Hogg, Dr Pierre Dilda, Associate investigators are Dr. Kerrie McDonald, Prof Minoti Apte and Prof. Ian Dawes ($2,250,000 over 5 years).
- The Cancer Institute NSW. Translational Program Grant 2007-2011. Project title: “Anti-mitochondrial cancer drugs”. Chief investigators are Prof. Philip Hogg, Prof. Robyn Ward, Prof. Ian Dawes, Dr. Richard Lock and Dr Paul de Souza ($3,750,000 over 5 years). Dr Pierre Dilda is associate investigator responsible for the preliminary data presented in the application (in vitro characterization of PENAO).
- The Cancer Council NSW. Research Program Grant 2006-2010. Project title: “New arsenical-based cancer drugs”.Chief investigators are Prof. Philip Hogg, Prof. Ian Dawes and Dr. Richard Lock ($3,800,000 over 5 years). Dr Pierre Dilda is associate investigator #1 responsible for the preliminary data of 2 out of 3 projects presented (tumour angiogenesis and acute promyelocytic leukemia).
- Faculty Research Grants
- Faculty of Medicine, University of New South Wales, Faculty Research Grant 2012. Project title: “Effects of an adamantane-type polyarsenic compound in drug-resistant ovarian cancers”. Chief investigator A: Dr Pierre Dilda; Chief investigator B: Dr Viola Heinzelmann-Schwarz ($20,000 for one year).
- Faculty of Medicine, University of New South Wales, Faculty Research Grant 2011. Project title: “Investigation of an arsenical-based metabolic inhibitor in glioblastoma”. Chief investigator A: Dr Pierre Dilda; Chief investigator B: Dr Kerrie McDonald; AI: Prof Philip Hogg; AI: Dr Charles Teo ($20,000 for one year).
- Faculty of Science Interdisciplinary Research Grant
Faculty of Science, University of New South Wales, Faculty of Science Interdisciplinary Research Grant 2015. Project title: "Development of polymeric nanoparticles for the co-delivery of two anti-cancer drugs for the treatment of sarcoma". Chief investigator A: Prof Martina Stenzel; Chief investigator B: A/Prof. Jia-Lin Yang; Chief investigator C: Dr Pierre Dilda ($5,000 + $20,000).
- Travel Grant
Australian Academy of Science. Travel Grant. “Scientific Visits to Europe 2009-2010”. Host: Prof. Pompella laboratory in Department of Experimental Pathology, University of Pisa Medical School, Italy. Project title: “Identification of cancer patients that will better respond to treatment with GSAO”.
Senior Research Fellow
- Cancer and Related Disorders