演題抄録

臓器別シンポジウム

開催概要
開催回
第51回・2013年・京都
 

A cure for metastatic breast cancer: how will we get there?

演題番号 : OS13-1

[筆頭演者]
Matthew J.C. Ellis:1 

1:Division of Medical Oncology, Washington University School of Medicine, USA

 

Metastatic breast cancer is an incurable disease. Treatment is guided by HER2 and ER expression, and the use of therapies directed against these therapeutic targets improves survival. Prolonged chemotherapy may be effective for sensitive patients but accumulating toxicity limits maintenance chemotherapy approaches. Currently available treatments for breast cancer are insufficiently efficacious. Deeper insights into fundamental processes driving treatment resistance are needed to develop more effective and potentially curative regimens.Next generation sequencing is beginning to suggest new therapeutic approaches that might be more effective (Cancer Discov 2013:3;27-34), most notable are HER2 mutations in HER2 non-over-expressed tumors which are the target of an ongoing neuratinib trial (Cancer Discov 2013:3;224 227). Other targets currently being exploited include the CDK4/CyclinD, the PI3K, and the BRCA-dependent DNA repair deficiency pathways. However there are no predictive biomarkers for the use of CDK4 inhibitors, rapalogs or PARP inhibitors. Aggressive application of next generation sequencing to samples taken in the advanced disease setting where the trials for these agents have been conducted is clearly a high priority. I will focus on the use of a patient-derived xenografts (PDX) system to derive the therapeutic principles for more effective systemic treatments. PDX models are available from HER2- and ER- disease at any stage of presentation, but for ER+ HER2- disease, most models are derived from advanced disease patients. We have demonstrated PDX are excellent genomic replicas (Nature 2010 464:999-1005) and most xenograft-specific mutations (due to mutational drift) are unlikely to be functionally significant. A series of PDX trials have been initiated with a wide spectrum of agents. Well powered PDX studies offer promising insights into treatment resistance and improved patient selection strategies and that could eventually lead to a cure.

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