The Parker laboratory explores interactions in the cancer microenvironment that prevent or support tumour invasion and spread (metastasis) to other tissues, including bone. Our overall objective is to uncover new biomarkers (genes/proteins) that predict risk of cancer metastasis and response to therapy and uncover novel precision therapeutic strategies to target the most lethal stages of solid cancer progression at an individual patient level. Our investigations integrate innovative science and pre-clinical research to inform the translation of agents into clinical trial.

Key investigative questions:

  • Can we predict the risk of local and distant cancer relapse in breast and prostate cancer at the time of diagnosis?
  • Can we prevent tumour cells from spreading by altering the microenvironment through therapeutic means?
  • Can we induce changes in tumour cells to enhance immunogenicity and impact the immune landscape?

(a) Stratification of breast cancer patients for proposed treatment regimens based on tumour interferon (IFN) signalling marker, IRF9. (b) Kaplan
Meier of breast cancer survival based of tumour expression of IRF9. (c) Immune profiling of an immune-reactive (hot) vs an immune poor (cold)
primary breast tumour (d) Decreased tumour burden in lung (mice) is associated with increased IFN-g production by tumour-specific T cells following
combination therapy with a checkpoint inhibitor (anti-PD-1) and IFN-inducer, Poly(I:C)

Research projects

Tumour microenvironment (TME) Interactions

From the loss of myoepithelial cell barriers in the transition from ductal carcinoma in situ to invasive carcinoma in breast cancer to the induction of tumour cell loss of immunogenicity markers during breast and prostate metastasis, our laboratory utilises both mouse and human systems in conjunction with cutting-edge techniques (robotic 3D systems, multiplex immunohistochemistry) to explore how interactions and cellular alterations in the TME shape cancer progression. We are currently evaluating how novel biomarkers that we have discovered through high-throughput RNA and protein screens in several stages of solid cancers can be exploited as identifiers and targets of tumour growth, invasion and spread.

Precision Therapy & Translation

We use various immune-activating compounds (HDAC inhibitors, viral mimetics, cytokine inducers) in different systems (in vitro, ex vivo & in vivo inc. PDX/explants) to investigate how we can promote long-term immune responses against tumour cells. Preclinical and retrospective patient studies enable us to assess the synergy of immune-targeted agents with conventional treatment, such as chemotherapy and hormone deprivation. We can also determine how patients may respond to therapy and stratify subsets of patients that may benefit from personalised treatment regimens through rigorous immune profiling.

Bone Metastasis

Several of our investigations have revealed the importance of tumour-intrinsic immune signaling pathways, particularly those drive by the type I interferon (IFN) family cytokines, in bone metastasis—a common site of tumour cell spread in both prostate and breast cancer that is currently incurable. Loss of this pathway in cancer cells can accelerate bone metastases and promotes changes in the osteoimmune TME to permit tumour expansion. Our continued research into how this loss can be both induced and reversed is critical to the promotion of tumour cell visibility in bone to immune effector cells and sustained tumour clearance.

People

Damien Zanker, Post Doc
Katie Owen, Post Doc
Natasha Brockwell, Post Doc
Alex Spurling, Research Assistant
Miriam Fuentes, PhD Student
Eden Febbraio, Honours Student

Key publications

1. Brockwell NK, ……..Parker BS. Tumor inherent interferon regulators as biomarkers of long-term chemotherapeutic response in TNBC. (2019), npj Precision Oncology, 3, 21

2. Duivenvoorden HM, ……O’Toole SA, and Parker BS. Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion. (2017), Journal of Pathology, 243, 496-509

3. Brockwell NK, Owen KL, Zanker D… Parker BS. Neoadjuvant Interferons: Critical for effective PD-1 based immunotherapy in TNBC. (2017), Cancer Immunology Research, 2017, 5, 871-884

4. Parker BS*, Rautela J, Hertzog P* (*Co-corresponding). Antitumour actions of type I interferons: implications for cancer therapy. (2016), Nature Reviews Cancer, 16(3), 131-44

5. Rautela, J, Baschuk…Parker, BS. Loss of host type-I IFN signaling accelerates metastasis and impairs NK cell anti-tumor function in multiple models of breast cancer. (2015), Cancer Immunology Research, 3(11), 1207-17

6. Bidwell BN, …. Hertzog P and Parker BS. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis via immune escape. (2012), Nature Medicine, 18(8), 1224-1231

7. Withana NP, …., Parker BS. Cathepsin B inhibition limits bone metastasis in breast cancer. (2012), Cancer Research, 72(5), 1199-209. Cover feature.

Research programs

Positions available

The Parker Lab is currently looking for a motivated PhD Student interested in breast or prostate cancer metastasis, immunology and therapeutic intervention. Applicants are warmly encouraged to send their CV, academic transcripts and key areas of interest to [email protected]