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

October 10, 2018

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 the prestigious international 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).
-end-
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).

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).

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.

Notes to editors:

(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.

RCSI

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.