Seminar Poster

Speaker:
Professor Caroline Dive
BPharm, PhD, FMedSCi,
Deputy Director & Clinical and Experimental Pharmacology Group Leader,
Cancer Research UK Manchester Institute,
The University of Manchester, United Kingdom

Abstract:
There is increasing agreement that minimally invasive biomarkers to monitor patients receiving targeted therapies have huge potential benefit. The rarity and heterogeneity of CTCs make them a technically demanding source of biomarkers but one that holds great promise as the technical challenges are met. Marker independent technology platforms are in development which will better assess CTC subpopulations but none so far have been fully validated for clinical trial use and treatment decision making. CTC enumeration with CellSearch (EpCam and cytokeratin positive CTCs) has prognostic significance in many epithelial tumours, and in diseases with prevalent CTCs such as small cell lung cancer (SCLC), the dynamic range of CTC number allows pharmacodynamic evaluation. Biomarkers based on multiplex protein analysis and FISH are also evaluable in CTCs if sufficient can be detected.

Developments in single CTC isolation and genomic profiling are increasingly reported by allowing insight to the biology of invasive tumour cells including cellular co-expression of cancer specific mutations. Prof. Caroline Dive will present our progress in DNA profiling of single SCLC CTCs, and how this approach may inform on heterogeneity, and via serial sampling, on mechanisms of drug resistance.

Most recently, the group developed lung cancer patient CTC derived mouse models (termed CDX). SCLC CDX models faithfully recapitulate patient drug responses and will be useful to test novel therapeutics. CDX are generated at patient presentation and for those patients who first respond and then relapse with drug resistant disease, the relapse blood sample can be used to generate a paired CDX. Alongside single CTC profiling, the CDX approach will allow a comprehensive analysis of acquired drug resistance to chemotherapy, the discovery of new drug targets and testing of targeted therapies and drug combinations. Prof. Dive will also describe recent research exploring vasculogenic mimicry in SCLC. 

Finally, Prof. Dive will present a case report on a patient whose blood sample contained no CellSearch CTCs yet generated a CDX model. CTC filtration of this patient’s blood revealed a high proportion of mesenchymal CTCs consistent with Epithelial to Mesenchymal Transition (EMT).

All are welcome.
For inquiries, please contact Ms. Begonia Yuen at 2632 2960 or Mr. Jonathan Lee at 3763 6005.