FLAGSHIP 1 Inflammation in Cancer

Flagship leaders: Dr Connie Diakos and A/ Prof Viive Howell

Former Research Fellow: Dr Kelly McKelvey

Flagship Leaders:

Conjoint Senior Lecturer, Northern Clinical School; Medical Oncologist, Royal North Shore Hospital.

Dr Connie Diakos

Laboratory Research Director, Bill Walsh Translational Cancer Research Laboratory

A/Prof Viive Howell

Former Research Fellow:

Sydney Vital Research Fellow and Sydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Sydney Medical School Northern

Dr Kelly McKelvey

Inflammation is now recognised as a cardinal feature of malignancy, contributing to the development of cancer, as well as being a consequence of the disease and its treatments. In established cancers, patients with evidence of systemic inflammation have demonstrated poorer outcomes and poorer response to treatment, with inferior anti-cancer effect and greater toxicities.

Local inflammation, i.e. that arising within the primary tumour, has positive prognostic outcomes, however, as the recruitment of immune and inflammatory cells into the tumour signify a heightened immune response to the malignancy, resulting in a positive anti-cancer benefit and lower systemic inflammation.

In this flagship, we aim to examine the following aspects of cancer-related inflammation:

  • Systemic vs local inflammation
  • Prognostic and predictive biomarkers
  • Amelioration of inflammation to improve patient outcomes
  • Treatment-related inflammation, including harnessing this for better anti-cancer benefit

Publications

 

“The intertwined fates of inflammation and coagulation in glioma” Cho, A., McKelvey, K., Lee, A. and Hudson, A.

“Radiation, inflammation and the immune response in cancer” Back, M., Diakos, C., Eade, T., Hudson, A., and McKelvey, K.

FLAGSHIP 2 Translational Theranostics

Flagship Leader: Prof Dale Bailey

Former Fellows:

Dr David ChanDr Aimee Hayes

Flagship Leader:

Professor of Medical Radiation Sciences, Principal Physicist at Royal North Shore Hospital

Prof Dale Bailey

Former Research Fellows:

Medical Oncologist

Dr Aimee Hayes

Medical  Oncologist, RNSH; Chair of the Neuroendocrine Tumours Group, COSA

Dr David Chan

“Theranostics” is the name given to an emerging methodology for imaging and delivering therapy with a single compound, usually a molecule, nanoparticle or a peptide (or vector). Usually, different labels are added to the vector for pre-therapeutic imaging and for therapy. Common examples of some of the labels used are radionuclides such as PET or SPECT imaging labels (e.g., Gallium-68, Technetium-99m, Iodine-124, Copper-64) and therapy with a beta particle emitting radionuclide (e.g., Iodine-131, Lutetium-177, Yttrium-90, Copper-67).  Other non-radionuclide labels that can be imaged are also available, such as fluorescent compounds. The imaging often serves to establish that the disease targeted by the therapy demonstrates sufficient uptake of the theranostic vector before proceeding with the treatment.

Flagship 2 focuses on bringing new theranostic pairs into clinical use by facilitating rapid translation from the design and pre-clinical testing phase into clinical trials & patient use. Current projects include:

  • the clinical management of neuroendocrine tumours (NETs) including the development of biomarkers, Quality of Life assessments and databases to assist in defining prognostic markers, collaborating with the Pharma industry to run first-in-man imaging trials of new theranostic radiolabel pairings and new peptide antagonists,
  • providing an appropriate trial framework for introducing new theranostics to examine their efficacy and applying new imaging methodologies to better inform treatment decisions (g., in lymphoedema, functional pituitary lesions, brain tumours),
  • developing new radiolabelled forms of anti-cancer pharmaceuticals to image with prior to therapy to demonstrate in vivo targeting,
  • studying the sequencing or combination of therapies combining chemotherapy and immunotherapy with a theranostic approach.

Publications

“Clinical and imaging-based prognostic factors in radioembolisation of liver metastases from colorectal cancer: a retrospective exploratory analysis.” Kathy P. Willowson, Aimee R. Hayes, David L. H. Chan, Michael Tapner, Elizabeth J. BernardRichard Maher, Nick Pavlakis, Stephen J. Clarke and Dale L. Bailey

“A Comparison of 2D and 3D Kidney Absorbed Dose Measures in Patients Receiving 177Lu-DOTATATE” Kathy P Willowson1, HyunJu Ryu, Price Jackson, Anita Singh, Enid Eslick, Dale L Bailey

FLAGSHIP 3: Nanotechnology

Flagship Leader: Prof Alexander Engel, Co-leaders: Prof Zdenka KuncicProf Ewa Goldys and Prof Mark Molloy

Current Research Fellow: Dr Yaser Gholami

Former Research Fellow: Dr Wei Deng ; Dr Hilary Byrne

 

Nano Medicine in Oncology: improved preoperative staging and better understanding of chemotherapy delivery n (T1-T2-T3).

Flagship Leaders:

Lawrence Penn Chair of Bowel Cancer Research Faculty of Medicine and Health Northern Clinical School, USYD

Prof Mark Molloy

Professor, Deputy Director, ARC Centre of Excellence for Nanoscale Biophotonics, Macquarie University

Prof Ewa Goldys

Professor of Physics, Founding Co-Director, Australian Institute for Nanoscale Science and Technology

Prof Zdenka Kuncic

Clinical Network Director, Cancer and Palliative Care Services, NSLHD Former Centre Director, Sydney Vital; Head of Colorectal Surgical Unit, RNSH, Professor of...

Prof Alexander Engel

Research Fellows:

Postdoctoral Scientist Nuclear Nanomedicine

Dr Yaser Gholami

Former Research Fellows:

Postdoctoral Scientist, Nanomedicine research.

Dr Hilary Byrne

Sydney Vital Research Fellow, Physics and Astronomy Department, Faculty of Science, Macquarie University

Dr Wei Deng

The broad purpose of Flagship 4 is to embed/define nanotechnology in oncology. The Flagship brings together several disciplines, some non-medical, across multiple sites and multiple partners to enhance capacity at SV. Its primary aim is to better define lymph-node metastasis in colorectal cancer with a view to developing a nanotechnology-based theranostic pathway. A secondary aim is to improve adenoma recognition at colonoscopy by developing a surface biomarker based nano-beacon.

Publications

“Nanoparticle radio-enhancement: principles, progress and application to cancer treatment” Zdenka Kuncic and Sandrine Lacombe

“Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol” A L McNamaraW W Y KamN ScalesS J McMahonJ W BennettH L ByrneJ SchuemannH PaganettiR Banati and Z Kuncic

“Cancer nanomedicine: challenges and opportunities” Zdenka Kuncic