New cancer marker may be key to tailored chemotherapy treatment in hard to treat breast cancer – Cancer vaccine target?

Dr Stephen Chan DM, FRCR, FRCP Consultant Oncologist Breast and Gynaecological Cancers Nottingham University Hospitals Trust Honorary Professor at the University of Nottingham Visiting Professor of Cancer Medicine at Nottingham Trent UniversityMedicalResearch.com Interview with: Dr Stephen Chan DM, FRCR, FRCP
Consultant Oncologist Breast and Gynaecological Cancers
Nottingham University Hospitals Trust
Honorary Professor at the University of Nottingham
Visiting Professor of Cancer Medicine at Nottingham Trent University

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Chan: Worldwide each year 1.68 million women are diagnosed with breast cancer and more than half a million die from the disease. Of these new cases around 12% will be classified as triple negative breast cancer (TNBC), meaning that tumour cells from these patients do not show any of the three established clinical markers that can be treated with targeted therapies. These drugs are used in addition to standard chemotherapy to improve the chance of a good treatment response, leading to prolonged disease free survival. Without these additional treatment options triple negative patients are forced to depend entirely on chemotherapy to treat their cancer.

Traditionally the sensitivity of a cancer to different types of chemotherapy has been categorised is based on a tumours tissue of origin and stage. There is currently no predictive marker of response that would allow chemotherapy treatment to be tailored to individual patients. With this information a clinician can predict which patients would benefit most from a particular chemotherapy and switch any who would do poorly to an alternative. The result would be a shift to increased treatment efficacy, while avoiding toxicity from ineffective treatment, which would in turn also reduce the cost to the health service. This need is particularly acute in triple negative breast cancer cases where chemotherapy is the cornerstone of treatment.

In collaboration with researchers based at Nottingham Trent University our group has been successful in finding new markers, which can predict how a patient will respond to chemotherapy treatment. One of these is HAGE (DDX43), a DEAD box RNA helicase. We have found that high HAGE expression predicts good respond to one of the main first line chemotherapy drugs, called anthracycline (Tarek MA Abdel-Fatah et al, April 2014). Our recent work (Tarek MA Abdel-Fatah, 2015) has shown that the predictive value is strong in triple negative breast cancer cases.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Chan: Because patients with TNBC are so reliant on chemotherapy to cure their cancer, it is important to choose the one that will be the most effective. Our results have shown that HAGE may be a good test for tailoring these patients chemotherapy, so that those who will respond well to anthracycline receive it and those who will not, go on to receive an alternative that may give them a better chance of a good response.

MedicalResearch: What are the possibilities for future research as a result of this study?

Dr. Chan: In the future a test kit for HAGE could be used to help guide clinical decision making for these patients. However it is likely that such a kit would include several markers in combination, to provide a complete profile of all the chemotherapy options. We have several other markers, awaiting publication, which could be combined in this way. Our long term goal for this research would be the development of a testing kit, as well as conducting a clinical trial to establish its clinical utility.

Going beyond testing for HAGE we have found that it can provoke an immune response, and that high expression is associated with the presence of tumour infiltrating lymphocytes. This indicates that HAGE may provide a potential target for a future cancer vaccine, and work is already under way to test this hypothesis.

Citations:

HAGE in triple negative breast cancer (TNBC) is a novel prognostic, predictive and actionable biomarker: A Transcriptomic and protein expression analysis

Authors: Dr. Tarek MA Abdel-Fatah, Dr. Stephanie E McArdle, Ms. Devika Agarwal, Mr. Paul M Moseley, Dr. Andrew R Green, Prof. Graham R Ball, Prof. A. Graham Pockley, Prof. Ian O Ellis, Prof. Robert C Rees, Prof. Stephen YT Chan

Journal: Clinical Cancer Research Impact Factor: 8.722

Published as Online First before final proofs on 3rd August 2015

Link: http://clincancerres.aacrjournals.org/content/early/2015/08/01/1078-0432.CCR-15-0610.abstract

Original clinical paper in British Journal of Cancer, published online on 22nd April 2014

Title: HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Authors: Tarek M.A. Abdel-Fatah, Stéphanie E.B. McArdle, Catherine Johnson, Paul M. Moseley, Graham R. Ball, A. Graham Pockley, Ian O. Ellis, Robert C. Rees, Stephen Y.T. Chan

Link: http://www.nature.com/bjc/journal/v110/n10/abs/bjc2014168a.html

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Editor’s notes:

Nottingham Personalised Therapy Oncology Research Group is led by Prof Stephen Chan and is focused on developing:

  • Cancer markers singularly and in combination, that can be used predict patient response to both chemotherapy and targeted treatments, such as Herceptin and Tamoxifen.
  • Cancer markers that can be developed as new drug targets.
  • Cancer immunology and cancer vaccines.

For further information on the research group please contact Paul Moseley at paul.moseley@nuh.nhs.uk

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Dr Stephen Chan DM, FRCR, FRCP (2015). New cancer marker may be key to tailored chemotherapy treatment in hard to treat breast cancer – Cancer vaccine target?