Abstract

Abstract Genetic and phenotypic heterogeneity of cancer cells within tumors underlies metastatic progression and therapeutic resistance, thus, it is a major clinical problem. We have characterized intratumor genetic and phenotypic heterogeneity by immunoFISH (iFISH) in primary tumor, lymph node, and distant metastases from the same patient and breast tumor biopsies before and after treatment. We found that distant metastases were highly divergent in some patients and that intratumor diversity associated with tumor subtype and response to treatment. We have also developed preclinical models to assess the functional relevance of intratumor heterogeneity in breast cancer and found cooperative clonal interactions that may promote metastatic progression and contribute to therapeutic resistance. In addition, our analyses of associations between clonal frequency and drivers of tumor growth have revealed some unexpected findings. Our results highlight the importance of exploring and understanding tumors at the single cell level to be able to predict and overcome disease progression and therapeutic resistance. Citation Format: Kornelia Polyak. Metastasis and diversity in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr IA1.

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