Triple negative breast cancer

Programme stream(s): Cancer discovery / underpinning research , Treatment
Programme session type(s): Bench to bedside

Chair: Adrian Harris, University of Oxford, UK
Speaker: Jean Abraham, University of Cambridge, UK
Speaker: Roger Daly, Monash University, Australia
Speaker: Peter Schmid, Barts Cancer Institute, UK

14:00-16:00

Room: Carron

The session will focus on triple negative breast cancer (TNBC), with speakers discussing the basic biology, recent translational work and clinical trials in this cancer subtype. Participants will gain a broad exposure to the fundamental mechanisms driving TNBC and some of the recent clinical applications of these discoveries. In particular, there will be a focus on recent clinical trial data in TNBC.

Identification of novel therapeutic targets for triple negative breast cancer through integrative kinomics
Speaker: Roger Daly
Affiliation: Department of Biochemistry and Molecular Biology, Monash University

Abstract:

Triple negative breast cancers (TNBCs) present a major clinical problem due to their aggressive nature and lack of effective targeted therapies. Consequently, there is a major need to identify therapeutic targets for this disease subgroup. We have addressed this problem via two programs of research that integrate mass spectrometry (MS)-based proteomics with functional genomic screens. In the first, MS-based tyrosine phosphorylation profiling subclassified a large TNBC cell line panel into distinct subgroups, and protein kinases exhibiting subgroup-selective activation profiles were identified by MS. Subsequent functional screens revealed opportunities for drug repurposing (eg specific FGFRs) and novel therapeutic targets. The second approach exploited our previous finding that TNBC is characterized by a prominent Src family kinase-dependent signalling network. Definition of the global impact of oncogenic Src on the expressed kinome, and then functional annotation of Src-regulated kinases, revealed several kinases essential for Src-induced transformation, including SGK1. In TNBC cells, Src positively regulated SGK1 expression and combined inhibition of Src and SGK1 was more effective than either treatment alone in inhibiting colony formation in vitro and tumour growth in nude mice. Therefore, this approach not only provides major mechanistic insights into oncogenic transformation but also aids the design of improved therapeutic strategies.