Featured Research

from universities, journals, and other organizations

Cancer scientists identify a new layer of complexity within human colon cancer: Shed light on resistance to treatment

Date:
December 13, 2012
Source:
University Health Network
Summary:
Cancer scientists have found a way to follow single tumor cells and observe their growth over time. The team discovered that biological factors and cell behavior -- not only genes -- drive tumor growth, contributing to therapy failure and relapse.

Cancer scientists led by Dr. John Dick at the Princess Margaret Cancer Centre have found a way to follow single tumour cells and observe their growth over time. By using special immune-deficient mice to propagate human colorectal cancer, they found that genetic mutations, regarded by many as the chief suspect driving cancer growth, are only one piece of the puzzle. The team discovered that biological factors and cell behaviour -- not only genes -- drive tumour growth, contributing to therapy failure and relapse.

Related Articles


The findings, published December 13 online ahead of print in Science, are "a major conceptual advance in understanding tumour growth and treatment response," says Dr. Dick, who holds a Canada Research Chair in Stem Cell Biology and is a Senior Scientist at University Health Network's McEwen Centre for Regenerative Medicine and Ontario Cancer Institute, the research arm of the Princess Margaret Cancer Centre. He is also a Professor in the Department of Molecular Genetics, University of Toronto. The research work was primarily carried out in Toronto by Antonija Kreso, Catherine O'Brien, and other members of the Dick lab with support from clinician-scientists at Mount Sinai Hospital and at the Ontario Institute for Cancer Research, and from genome scientists at St Jude Research Hospital, Memphis, and the University of Southern California, Los Angeles.

By tracking individual tumour cells, they found that not all cancer cells are equal: only some cancer cells are responsible for keeping the cancer growing. Within this small subset of propagating cancer cells, some kept the cancer growing for long time periods (up to 500 days of repeated tumour transplantation), while others were transient and stopped within 100 days. They also discovered a class of propagating cancer cells that could lie dormant before being activated. Importantly, the mutated cancer genes were identical for all of these different cell behaviours.

When chemotherapy was given to mice in which the human tumours were growing, the team made the unexpected finding that the long-term propagating cells were generally sensitive to treatment. Instead, the dormant cells were not killed by drug treatment and became activated, causing the tumour to grow again. The cancer cells that survived therapy had the same mutations as the sensitive cancer cells proving that cellular factors not linked to genetic mutation can be responsible for therapy failure.

The research challenges conventional wisdom in the cancer research field that the variable growth properties and resistance to therapy of cancer cells are solely based on the spectrum of genetic mutations within a tumour, says Dr. Dick. Instead, the scientists have validated a developmental view of cancer growth where other biological factors and cell functions outside genetic mutations are very much at play in sustaining disease and contributing to therapy failure.

The new research published builds on decades of experience by Dr. Dick, who focuses on understanding the cellular processes that maintain tumour growth. In 2004, Dr. Dick published related findings in leukemia, but in the present study his team was able to compare the importance of genetic events with cellular mechanisms for the first time. It is also the first study of its kind in a solid tumour system.

Dr. Dick says the findings convinced him that the conventional view that only explores gene mutations is no longer enough in the quest to accelerate delivery of personalized cancer medicine to patients -- targeted, effective treatments customized for individuals.

"The data show that gene sequencing of tumours to find the spectrum of their mutations is definitely not the whole story when it comes to determining which therapies will be most effective," says Dr. Dick.

"This is a paradigm shift that shows research also needs to focus on the biological properties of cells. For example, finding a way to put dormant cells into growth cycles could make them more sensitive to chemotherapy treatment. Targeting the biology and growth properties of cancer cells could expand the repertoire of usable therapeutic agents and provide better outcomes for patients."


Story Source:

The above story is based on materials provided by University Health Network. Note: Materials may be edited for content and length.


Journal Reference:

  1. Antonija Kreso, Catherine A. O’Brien, Peter van Galen, Olga Gan, Faiyaz Notta, Andrew M. K. Brown, Karen Ng, Jing Ma, Erno Wienholds, Cyrille Dunant, Aaron Pollett, Steven Gallinger, John McPherson, Charles G. Mullighan, Darryl Shibata, and John E. Dick. Variable Clonal Repopulation Dynamics Influence Chemotherapy Response in Colorectal Cancer. Science, 13 December 2012 DOI: 10.1126/science.1227670

Cite This Page:

University Health Network. "Cancer scientists identify a new layer of complexity within human colon cancer: Shed light on resistance to treatment." ScienceDaily. ScienceDaily, 13 December 2012. <www.sciencedaily.com/releases/2012/12/121213142309.htm>.
University Health Network. (2012, December 13). Cancer scientists identify a new layer of complexity within human colon cancer: Shed light on resistance to treatment. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2012/12/121213142309.htm
University Health Network. "Cancer scientists identify a new layer of complexity within human colon cancer: Shed light on resistance to treatment." ScienceDaily. www.sciencedaily.com/releases/2012/12/121213142309.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins