Surgical Oncology Research Group

Sarcoma and Nano-oncology Group

About us

Sarcoma and Nano-oncology Research Group (SNRG) is the experimental cancer research team in the Integrated Cancer Research component of the Adult Cancer Program, located in the Lowy Cancer Research Centre (LCRC). The SNRG focuses on basic and translational studies using current technologies to improve diagnosis and treatment of human sarcomas and other epithelial cancers.

Sarcomas are connective tissue tumours account for nearly 15-20% of childhood cancers and 1-2% adult cancers. About 50% of patients diagnosed with sarcoma eventually die of the disease, regardless of standard treatment including surgery, radiotherapy and chemotherapy. Application of nanobiotechnology in oncology has resulted in revolution in cancer research and practice. The SNRG specifically focuses on improving the diagnosis of sarcoma and other epithelial cancers and the efficacy of radiotherapy, chemotherapy, targeted therapy and surgery using nanoparticle-based technology. We aim to translate effective new treatments into clinical trials, eventually affecting clinical practice and policy. The group is involved in extensive collaborative projects both in Australia and internationally.

The group is led by co-directors, Prof Phil Crowe and A/Prof Jia Lin Yang.

Prof Crowe is the current Chairman of the Department of Surgery at the Prince of Wales Clinical School (POWCS), Faculty of Medicine, University of New South Wales. He was the founder and has been the director of the Sydney Sarcoma Unit (www.sarcoma.org.au). He serves as a board member of the Australian Sarcoma Group (www.australiansarcomagroup.org). He is also a member of the Scientific Advisory Committe and Tissue Network Committee of the Australian Sarcoma Study Group (ASSG).

A/Prof Yang, is the team leader of the SNRG based at the Adult Cancer Program, Lowy Cancer Research Centre. He is a teaching and research academic of the POWCS and a senior scientist with clinician (rheumatology) and statistician background. He is the course convenor of Cancer Sciences (PATH3208), the course co-convenor of Cancer Sciences for Excercise Physiology (HESC3208), and Phase I Facilitator for Foundations (MFAC1501) and Beginnings, Growth and Development B (MFAC1522) of Faculty of Medicine. Apart from teaching undergraduate students at both School of Medical Sciences and School of Medicine, he has contributed in research leadership and supervision, biostatistics support, and administration, serving as the member of the Institute of Biosafety Committee of the University of New South Wales, and the member of the Scientific Advisory Committee of the Australian Sarcoma Study Group.

2015 Highlights

Cancer research

[1] Nano-oncological studies in sarcoma

Application of nanotechnology in oncology has been revolutionary in cancer research and practice. For example, there is a trend that nanoparticles will become a general carrier for anticancer drugs including conventional chemotherapeutics, targeted therapeutics, anti-metabolic agents and microRNAs. Nanooncological study is a multi-disciplinary collaborative one, which requires knowledge, skills, resources and financial support.

[2] Antimitochondrial therapy in sarcoma

Cancer cells catabolise nutrients in a different way than healthy cells. Healthy cells mainly rely on oxidative phosphorylation, while cancer cells employ aerobic glycolysis. Glucose is the main nutrient catalysed by healthy cells, while cancer cells often depend on catabolism of both glucose and glutamine. A key component involved in this altered metabolism is mitochondria. Mitochondria coordinate the catabolism of glucose and glutamine across cancer cells. Targeting mitochondrial metabolism in cancer cells has potential for the treatment of this disease. An antimitochondrial drug known as PENAO was synthesised at UNSW and proved to have an anti-tumour growth effect on many solid tumour cell lines, including a fibrosarocoma cell line, HT1080. The drug is currently under clinical trials for epithelial cancer, such as colon cancer. We are going to measure the effect of the drug in 3 fibrosarcoma cell lines in the laboratory and in a mouse model of fibrosarcoma. If successful, this study can be immediately translated to clinical trials.

[3] Identifying aberrant gene regulatory networks in soft tissue sarcoma

Sarcomas are aggressive and have a limited response to chemotherapy. Based on the cancer stem cell theory, sarcomas may arise from incompletely differentiated mesenchymal stem cells (MSCs). Since gene regulatory networks are known to play a key role in maintenance of MSC pluripotency, self-renewal and lineage commitment, we hypothesise that the gene regulatory circuits in sarcomas mimic MSCs rather their differentiated counterparts.

The aim of this project is to investigate gene regulatory networks in MSCs and soft tissue sarcoma. This project will first focus on the study of miRNA and will compare and contrast their expression between MSCs, differentiated cells and corresponding sarcomas. Differentially expressed miRNAs have been identified from sarcomas and differentiated tissue, however comparisons between MSCs and sarcomas have been limited and not performed on a genome-wide scale within a single study. Through this project, it is anticipated that a comprehensive understanding of altered miRNA/TF expression and gene regulatory network in sarcomas will be developed. This has the potential to enable the identification of novel biomarkers, prognostic tools and targeted therapies for sarcoma patients.

A new proposal for The Ross Trust (2014-2015) on MicroRNA and sarcoma is submitted together with this report. Further support from The Ross Trust will promote this study from the bioinformatical inference stage to the biological verification stage.

[4] PTEN study in sarcoma

Phosphatase and tensin homolog (PTEN) is a protein that is encoded by the PTEN gene. PTEN acts as a tumour suppressor gene. Mutations of PTEN cause the resulting protein to be nonfunctional or absent. The defective protein results in the host cell dividing in an uncontrolled way, which can lead to the growth of tumours. Our previous Ross Trust supported studies indicated that [1] activated EGFR is an independent marker of overall survival in sarcoma patients, [2] EGFR was expressed by all 13 sarcoma call lines detected, and [3] EGFR inhibitor monotherapy was insensitive in some sarcoma cell lines. We hypothesised that dysfunction of PTEN may be one of mechanisms of EGFR inhibitor resistance. The principle aim of this study is to detect the genetic and epigenetic expression of PTEN in a panel of 10 sarcoma cell lines and to determine the effect of targeted therapy using a PTEN signalling inhibitor in sarcoma cell lines. Specific objectives are [1] to characterise protein, mRNA and DNA expression of PTEN in a panel of sarcoma cell lines, [2] to measure growth inhibitory effect of the PTEN signalling inhibitor alone or combination with an EGFR inhibitor on the cell lines, and [3] to investigate potential mechanism of drugs action behind.

[5] Identification of key and strategic targets for cancer therapy

Our targeted therapy has focused on growth factor receptors (e.g. EGFR/HER) and their down-stream signalling transducers (eg. ERK, Akt, STAT1 and STAT3).

Cancer education

A Cancer Sciences (PATH3208) course was successfully run by the Prince of Wales Clinical School from Session II, 2012. Course outline can be found on the School of Medical Sciences website. A new undergraduate course, Cancer Sciences for Excercise Physiology (HESC3208) was created and successfully run in Session II, 2014 by both the POWCS and the School of Medical Sciences.

Click here to view the course manual.

Current Projects

  • Application of nanotechnology
  • Effect and mechanism of concurrent inhibition of HER family receptors and STAT3 in treatment of sarcoma
  • Effect and mechanism of concurrent inhibition of EGFR and metabolic in treatment of sarcoma
  • Inhibition of ALT associated protein in treatment of sarcoma
  • Bioinformatic and biological investigation of miRNAs in liposarcoma

For more information, please visit http://www.sarcoma.org.au/.

Team

Projects

Collaborators

In cancer research:     

  • Prof Elise C. Kohn, National Cancer Institute, NIH
  • A/Prof Xuchuan Jiang, Department of Chemical Engineering, Monash University
  • Prof Martina Stenzel, Centre for Advanced Macromolecular Design, Faculty of Science
  • Prof Michael Friedlander, Medical Oncology, POWH
  • Dr Michael Jackson, Radiation Oncology, POWH
  • Prof William R Walsh, S&ORL, POWH
  • A/Prof Yan Yu, S&ORL, POWH
  • Dr Ramon L Varcoe, POWPH
  • Prof Phil Hogg, Allosteric Disulphide Group, ACP, Lowy
  • Dr Pierre Dilda, Cancer Drug Development Group, ACP, Lowy
  • Dr Jason Wong, Bioinformatics and Protein Mass Spectrometry Group, ACP, Lowy
  • Dr Vashe Chandrakanthan, Stem Cell Group, ACP, Lowy

In cancer education:

  • A/Prof Julian Cox, Faculty of Science
  • Dr Patsie Polly, School of Medical Sciences
  • Ms Rachel Thompson, School of Medicine
  • Ms Kathryn Coleman, Deakin University, Melbourne
  • Ms Suzanne Mobbs, School of Medicine
  • Dr Zack Belinson, Computer Science and Engineering
  • Ms Fiona Naumann, School of Medical Sciences
  • Ms Lila Azouz, Blended Learning Developer, Faculty of Medicine

Grants & Funding

Grants (2013-2015)

1. The Ross Trust, 2013-2015, to PJ Crowe, JL Yang and D Goldstein

2. 1044795 /RG13-01 Targeting the stroma in pancreatic cancer – a novel therapeutic approach focusing on the HGF/c-MET pathway. M Apte, JS Wilson, D Goldstein, RC Pirola, RK Kumar Cancer Council NSW 2013-2015.

3. Rural Health Continuing Education Grant 2013-2014, JL Yang, Co-chief Investigator.

4. TCRN Conference & Professional Development Grants, 2013 to JL Yang

5. ASSG Research Meeting Travel Fund, 27 June 2014, Park Royal Hotel, Melbourne to XC Wang

6. ASSG Dr Andrew Baker Travel Fellowship 2014 for AACR Annual Meeting, 5-9 April 2014, San Diego, US to XC Wang

7. Postgraduate Research Support Scheme (PRSS), Graduate Research School, UNSW 2013 for Molecular Targets and Cancer Therapeutics, 19-23 October, 2013, Hynes Convention Centre, Boston, MA, US to XC Wang

8. POWCS semester 2 travel grant, UNSW 2013 for Molecular Targets and Cancer Therapeutics, 19-23 October, 2013, Hynes Convention Centre, Boston, MA, US to XC Wang

9. Rainbows for Kate PhD Scholarship from Australian Sarcoma Study Group (2013-2015) to XC Wang

10. UNSW Sarcoma Research Scholarship, 2014-2016 to R Ryan