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Chromosomal instability may predict patients that will benefit from colorectal cancer drug

Research aims to make sure that patients only receive drugs that will work specifically for their own disease

Date:
October 10, 2018
Source:
RCSI
Summary:
Researchers have discovered that chromosomal instability (where whole human chromosomes or parts of chromosomes are duplicated or deleted) may predict which patients will receive most benefit from a key drug used to treat colorectal cancer (Avastin).
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Researchers at RCSI, along with international collaborators within the ANGIOPREDICT research consortium, have discovered that chromosomal instability (where whole human chromosomes or parts of chromosomes are duplicated or deleted) may predict which patients will receive most benefit from a key drug used to treat colorectal cancer (Avastin). By knowing in advance which patients would not benefit from Avastin, individuals could be spared the side-effects of the drug, and are more likely to receive 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 journal Nature Communications. It marks a further important advance in the global effort to move towards a more personalised treatment approach for colorectal cancer patients.

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).

Speaking on the significance of the discovery, Professor Annette Byrne, Associate Professor at RCSI's Department of Physiology and Medical Physics said: "We have drawn on knowledge emerging from global efforts to characterise the complex genetic alterations that underpin the progression of colorectal cancer. We have demonstrated that tumours with intermediate-to-high chromosomal instability have improved outcome after Avastin treatment, whereas tumours characterised by low chromosomal instability benefit less. 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," added Professor Lambrechts (VIB-KU Leuven Center for Cancer Biology).

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 Professor Darran O'Connor (RCSI Department of Molecular and Cellular Therapeutics).


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Materials provided by RCSI. Note: Content may be edited for style and length.


Journal References:

  1. Dominiek Smeets, Ian S. Miller, Darran P. O’Connor, Sudipto Das, Bruce Moran, Bram Boeckx, Timo Gaiser, Johannes Betge, Ana Barat, Rut Klinger, Nicole C. T. van Grieken, Chiara Cremolini, Hans Prenen, Massimiliano Mazzone, Jeroen Depreeuw, Orna Bacon, Bozena Fender, Joseph Brady, Bryan T. Hennessy, Deborah A. McNamara, Elaine Kay, Henk M. Verheul, Neerincx Maarten, William M. Gallagher, Verena Murphy, Jochen H. M. Prehn, Miriam Koopman, Cornelis J. A. Punt, Fotios Loupakis, Matthias P. A. Ebert, Bauke Ylstra, Diether Lambrechts, Annette T. Byrne. Copy number load predicts outcome of metastatic colorectal cancer patients receiving bevacizumab combination therapy. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-06567-6
  2. Erik van Dijk, Hedde D. Biesma, Martijn Cordes, Dominiek Smeets, Maarten Neerincx, Sudipto Das, Paul P. Eijk, Verena Murphy, Anna Barat, Orna Bacon, Jochen H.M. Prehn, Johannes Betge, Timo Gaiser, Bozena Fender, Gerrit A. Meijer, Deborah A. McNamara, Rut Klinger, Miriam Koopman, Matthias P.A. Ebert, Elaine W. Kay, Bryan T. Hennessey, Henk M.W. Verheul, William M. Gallagher, Darran P. O'Connor, Cornelis J.A. Punt, Fotios Loupakis, Diether Lambrechts, Annette T. Byrne, Nicole C.T. van Grieken, Bauke Ylstra. Loss of Chromosome 18q11.2-q12.1 Is Predictive for Survival in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab. Journal of Clinical Oncology, 2018; 36 (20): 2052 DOI: 10.1200/JCO.2017.77.1782

Cite This Page:

RCSI. "Chromosomal instability may predict patients that will benefit from colorectal cancer drug." ScienceDaily. ScienceDaily, 10 October 2018. <www.sciencedaily.com/releases/2018/10/181010105559.htm>.
RCSI. (2018, October 10). Chromosomal instability may predict patients that will benefit from colorectal cancer drug. ScienceDaily. Retrieved December 8, 2024 from www.sciencedaily.com/releases/2018/10/181010105559.htm
RCSI. "Chromosomal instability may predict patients that will benefit from colorectal cancer drug." ScienceDaily. www.sciencedaily.com/releases/2018/10/181010105559.htm (accessed December 8, 2024).

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