Breast Cancer
Breast Cancer

Workpackage 2:

Small indication: Her2-therapy resistant metastatic breast cancer

Workpackage Leader

Prof. Dr. Klaus Pantel

 

Klaus Pantel

 

Uniklinikum Eppendorf

Workpackage Co-Leader


Dr. Jürgen Braunger

Objectives of the Workpackage

 

Workpackage 2 has four major objectives:

 

    • Setup of SOPs for molecular analysis
    • Functional evaluation of viable CTCs
    • Comparison of the SOPs between WP2 and WP1
    • Validation of the selected methods in HER2-positive breast cancer patients who failed to respond to anti-HER2 standard of care therapies

    Description of the tasks

     

    In breast cancer there is an urgent need for improved biomarkers, regarding residual risk assessment and potential benefit fof personalized treatment strategies. As a prime example of the effectiveness of molecularly targeted therapies, HER2-targeting agents have dramatically altered the natural history of HER2-positive breast cancer patients. The HER2-protein is a well-described marker where the metrics for HER2-expression/amplification on primary breast carcinomas have been correlated with response to HER2-targeting drugs such as trastuzumab or lapatinib. However, a significant fraction of patients with HER2-positive breast cancer treated with those agents eventually relapse or develop progressive disease. Therefore, the CANCER-ID consortium will focus on mechanisms of intrinsic and/or acquired resistance to HER2-targeted therapies. Intrinsic and acquired resistance to HER2-targeted therapies represents an eminent medical problem, imposing an urgent need for the development of novel companion diagnostic biomarker assays for early detection of resistance. At the same time these patients represent an ideal group for the establishment and validation of novel methods used for blood-based biomarker decisions.

    We will use the liquid biopsy approach to monitor HER2-positive breast cancer patients in order to evaluate different molecular aberrations related to HER2-resistance by performing serial enumeration and molecular characterization of CTCs as well as prospective sequential profiling of cfDNA and/or circulating miRNAs. We will develop highly sensitive and specific methods for the molecular characterization of these liquid biomarkers. Our goal is to evaluate and compare different technologies for molecular characterization and to establish technically and clinically validated methodologies documented in SOPs. We will also focus on the analysis of established pathways that can confer resistance to HER2-inhibitors. Analyses will include mutational analyses, establishment of copy number profiles, methylation and expression patterns, and miRNA analyses. Our findings will help to answer the key question whether treatment decisions based on the analyses of liquid biomarkers will lead to a measurable benefit in clinical outcome for cancer patients.

     

    >> WP 3: Data Management and Bioinformatics

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