1. Save the Date

2. The emerging role of circulating tumour cells and circulating tumour DNA in clinical oncology  
Paul de Souza
Foundation Professor of Medical Oncology, Western Sydney University
Conjoint Professor, UNSW
Liverpool Hospital
Ingham Institute for Applied Medical Research

3. CTCs in Prognosis and Progression
CTC number in 7.5 ml blood of metastatic breast cancer patients and correlation with survival (CellSearch)
CTC numbers increase with progression
Thalgott et al. 2013, J Cancer Res Clin Oncol
Cristofanili et al. 2004, N Engl J Med,

4. Circulating Tumor Cells (CTCs)
CTCs released by solid cancers
CTCs travel with the blood stream
May form distant daughter tumours

5. CTCs Isolation & Analysis
Sample inlet well
Wash well
Waste well
Isolation zone/ Cell spot cap
Recovery tube
Microfluidic Flow Channel
CTC
Lympho-
cyte
IsoFlux (Fluxion)

6. CTCs Isolation & Analysis
Picking module
Destination plate(s)
Sample
Microfluidic Spiral Device
ALS CellCelector
Tony Pang, Majid Ebrahimi, Therese Becker, Minoti Apte

7. Circulating Tumour Cells

8. Potential application of Liquid Biopsies
Diagnosis
Picking patients (prognostic, predictive)
Picking treatment approaches (surgery, RT, systemic)
Monitoring disease course
Disease biology
Treatment sensitivity vs treatment resistance
Clinical pharmacology
Mechanism of action (PARP, ARV7 assays in our Phase I trials unit)
Clinical trials translational research

9. Real-time monitoring of mutant sub-populations during therapy
“The right drug to the right patient at the right time”

10. Current Projects Melanoma Prostate Cancer Breast Cancer
Colorectal Cancer
Ovarian Cancer
Glioblastoma
Lung Cancer
Pancreatic Cancer
Gastric Cancer

11. Epithelial-Mesenchymal Transition (EMT) & Chemoresistance
Evidence suggests EMT
promotes formation of CTCs
can assist cancer cell survival
Importantly: EMT CTCs potentially contribute to chemoresistance

12. Tumour Biomarkers for Personalized Therapy
Liquid Biopsy biomarker screening (CTCs, ctDNA etc.) is a non-invasive, repeatable, way to identify “actionable” biomarkers
Biopsies of tumors on a repeated basis are invasive / costly / not possible
Biopsies may not be informative (tumour heterogeneity)
Biopsies are retrospective, unless repeated
Current use of Liquid Biopsies in Liverpool FTIH Phase I trials – PARP, ARV7
Gerlinger et al.

13. Summary
CTCs and ctDNA (liquid biopsy) is transforming the way medical oncology is currently practiced today
CTCs are an effective platform for discovery of new biomarkers for the development of companion diagnostics for new targeted therapies
CTCs can define tumour heterogeneity and identify mutant sub-populations
Liquid biopsy (CTCs, ctDNA, other) can be used to predict treatment response and monitor treatment course
The CCDR is at the forefront of this translational research and is leading the way in NSW
Give practical examples after each statement – hopefully using local examples in Liverpool (Across the road).

14. Acknowledgements / Funding
Collaborators
Various CTC projects
Patsy Soon
Bavanthi Balakrishnar
Scott McKenzie
Anna de Fazio
Wei Chua
Weng Ng
Tara Roberts
Minoti Apte
Tony Pang
Majid Ebrahimi
Therese Becker
Joseph Po
David Lynch
Yafeng Ma
Francis Young
Alison Luk
Pei Ding
Casey Borthwick
Colorectal CTC projects
Kevin Spring
Stephanie Lim
Puneet Singh
Emilia Ip
Ben Harris
Australian Rotary Health
Gynaecological Oncology PhD Scholarship

15. Save the Date