Metastasis is the fatal hallmark of cancer. Diversity within or between tumours and metastases that develops during disease progression is a serious hurdle for therapy. So it is crucial for the success of personalized cancer therapy to understand the cellular and molecular processes that underlie both intra-patient tumour heterogeneity and metastasis.
    Researchers in Switzerland used transcriptional profiling of tumours and matched metastases in patient-derived xenograft models in mice, the result showed cancer-site-specific phenotypes and increased glucocorticoid receptor activity in distant metastases. The glucocorticoid receptor mediates the effects of stress hormones, and of synthetic derivatives of these hormones that are used widely in the clinic as anti-inflammatory and immunosuppressive agents. The study shows that the increase in stress hormones during breast cancer progression results in the activation of the glucocorticoid receptor at distant metastatic sites, increased colonization and reduced survival.
    Proteomics and phospho-proteomics studies implicate the glucocorticoid receptor in the activation of multiple processes in metastasis and in the increased expression of kinase ROR1, both of which correlate with reduced survival. The ablation of ROR1 reduced metastatic outgrowth and prolonged survival in preclinical models.
    Results indicate that the activation of the glucocorticoid receptor increases heterogeneity and metastasis, which suggests that caution, is needed when using glucocorticoids to treat patients with breast cancer who have developed cancer-related complications.