10:23pm Tuesday 23 October 2018

Scientists identify chromosomal instability as a novel predictive biomarker for cancer drug Avastin

Following a recent publication in the leading cancer  journal Journal of Clinical Oncology RCSI and international collaborators within the ANGIOPREDICT research consortium have now  further revealed chromosomal instability  (where  whole human chromosomes or parts of chromosomes are duplicated or deleted) may predict which patients benefit most from the use of a key drug to treat colorectal cancer (Avastin). By predicting the patients that would not benefit from Avastin, individuals could be spared the side-effects of this particular drug therapy, and are more likely to receive an optimal treatment with a minimum of delay, while reducing cost of care.

The study, led by researchers at RCSI (Royal College of Surgeons in Ireland) and the VIB-KU Leuven Center for Cancer Biology in Belgium   is published this month in the prestigious international journal Nature Communications, and is a further important step in the global effort to move towards a more personalised treatment approach for colorectal cancer patients.

Speaking on the significance of the discovery, Professor Annette Byrne, Associate Professor at RCSI’s Department of Physiology and Medical Physics said: ‘In this study, we have drawn on knowledge emerging from global efforts to characterize the complex genetic alterations that underpin  the disease trajectory of colorectal cancer. We have demonstrated that tumours with intermediate-to-high chromosomal instability have improved outcome after Avastin treatment, whereas tumours characterized by low chromosomal instability derive reduced benefit. This work further builds on our recent Journal of Clinical Oncology study and  has  identified a complementary biomarker strategy that could be used by doctors in the future to distinguish between patients who will benefit from Avastin, and patients who will not respond.’

‘As always, our overall goal is to improve the standard-of-care for colorectal cancer and to make sure  that patients only receive drugs that will work specifically in the setting of their own disease. This will reduce side-effects, treatment costs and improve patient outcomes,’ Professor Byrne added.

The international research team was led in Ireland by Professor Byrne (RCSI) and in Belgium (VIB-KU Leuven) by Prof Diether Lambrechts. The team analysed genetic alterations from archival tumour samples for patients with advanced colorectal cancer for which the complete disease course was known. Patients with tumours that demonstrated intermediate to high levels of chromosomal instability responded better to Avastin treatment than those patients with low levels of chromosomal instability. Joint first authors on the paper are Dr Dominiek Smeets (VIB-KU Leuven), Dr Ian Miller (RCSI Department of Physiology and Medical Physics) and Prof Darran O’Connor (RCSI Department of Molecular and Cellular Therapeutics).

According to the World Cancer Research Fund, colorectal cancer is the third most common cancer worldwide with nearly 1.4 million new cases diagnosed annually (1). In 2014, almost 153,000 people died from colorectal cancer in the EU equivalent to 11 per cent of all deaths from cancer. (2). Half of colorectal cancer patients develop metastatic cancer, where the cancer spreads to other parts of the body, for which Avastin is a key component of therapy (3).

RCSI is ranked among the top 250 (top 2%) of universities worldwide in the Times Higher Education World University Rankings (2018) and its research is ranked first in Ireland for citations. It is an international not-for-profit health sciences institution, with its headquarters in Dublin, focused on education and research to drive improvements in human health worldwide. RCSI is a signatory of the Athena SWAN Charter

Publication
The full research article is available online here.

Reference
(1) Source: World Cancer Research Fund, 2012
(2) Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E. and Forman, D. (2011), Global cancer statistics. CA: A Cancer Journal for Clinicians, 61: 69–90. doi: 10.3322/caac.20107
(3) Strickler JH, Hurwitz HI. Bevacizumab-based therapies in the first-line treatment of metastatic colorectal cancer. Oncologist. 2012;17(4):513-24. Epub 2012 Apr 3. PubMed PMID: 22477726.

Funding
In 2012 the ANGIOPREDICT (angiopredict.com) research consortium, led by Professor Annette Byrne at RCSI, received approximately €6 million in competitive funding from the European Commission’s Seventh Framework ‘Health’ Programme (FP7).

 

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