Intratumoral heterogeneity and drug response in high-grade serous carcinoma

Abstract:

Abstract Our understanding of the molecular basis of epithelial ovarian cancer has changed dramatically over the past 10 years. We now recognise that different histological subtypes are fundamentally different diseases, based on recent discoveries identifying the cell-of-origin and key driver mutations for high-grade serous (HGSOC) and clear cell ovarian cancers. The major challenge for the development of personalized treatment for HGSOC is the extreme genomic heterogeneity between cases and additional intratumoural heterogeneity (ITH). We have previously shown that HGSOC is characterised by ubiquitous TP53 mutation and we have proposed that early loss of TP53 may be permissive for the development of a wide range of mutator phenotypes, which may contribute to platinum resistance and ITH. I will discuss our recent findings showing profound ITH in HGSOC and how tandem mutator phenotype may alter evolution in HGSOC. We have developed new methods to identify and quantify circulating tumour DNA in plasma samples from women with HGSOC. These methods provide highly specific biomarkers of response to treatment and can be used to track the emergence of resistant clonal populations. Application of these methods in a national study of relapsed ovarian cancer and in new clinical trials will provide critical clinical data to develop personalized treatment strategies for women with HGSOC. Citation Format: James D. Brenton. Intratumoral heterogeneity and drug response in high-grade serous carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr IA19.

Authors:

JD Brenton

Journal:

Clinical Cancer Research

Citation info:

19(19_Supplement):ia19-ia19

Publication date:

1st Oct 2013

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