Featured Research

from universities, journals, and other organizations

Researchers detail possible resistance mechanisms of colorectal cancer to bevacizumab (avastin)

Date:
October 28, 2013
Source:
University of Colorado Cancer Center
Summary:
A study published shows that when colorectal cancer is targeted by the drug bevacizumab (Avastin), tumors may switch dependence from VEGF-A, which is targeted by the drug, to related growth factors in including VEGF-C, VEGF-D and placental growth factor. This change to new growth-factor dependence may allow colorectal cancer to push past bevacizumab’s blockage of VEGF-A to continue to drive tumor growth.

A University of Colorado Cancer Center study published in the journal PLoS One shows that when colorectal cancer is targeted by the drug bevacizumab (Avastin), tumors may switch dependence from VEGF-A, which is targeted by the drug, to related growth factors in including VEGF-C, VEGF-D and placental growth factor. This change to new growth-factor dependence may allow colorectal cancer to push past bevacizumab's blockage of VEGF-A to continue to drive tumor growth.

Related Articles


"Think of it like damming a river. Bevacizumab can block the main flow, but then once a tumor's need builds up behind this dam, water starts to flow around the blockage in the form of streams and tributaries. That's like these other growth factors -- eventually a tumor becomes able to use these tributaries of VEGF-C, VEGF-D and placental growth factor to supply itself with the 'water' it needs," says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of Medical Oncology at the University of Colorado School of Medicine.

The analogy of liquid is an apt one -- bevacizumab slows cancer's growth by limiting a tumor's ability to grow the new blood vessels it needs to supply itself with nutrients. Especially in combination with chemotherapy, bevacizumab has proved an effective treatment for colorectal cancer. But then there frequently comes a point at which bevacizumab stops working and the tumor restarts its growth. This study asked why.

Specifically, Lieu and colleagues serially tested the levels of other VEGF-related growth factors in 42 patients treated with bevacizumab and chemotherapy, at many points during the course of their treatment.

"What we saw is that levels of VEGF-C and placental growth factor went up just before tumors progressed and then stayed high during the periods of tumor growth. Interestingly, VEGF-D was only elevated during progression. But it seems that tumors may be using these growth factors as ways to create blood vessel growth in the absence of VEGF-A, blocked by bevacizumab," Lieu says.

Then the researchers also took a snapshot of levels in 403 colorectal cancer patients, at one time during treatment. Because this group included patients who were and were not being treated with chemotherapy along with bevacizumab, they could show that the rise in VEGF levels was, in fact, due to bevacizumab and not to some interaction with the chemotherapy.

"It's too early to say with certainty that VEGF-C, VEGF-D, and placental growth factor are the cause of colorectal cancer resistance to bevacizumab, but the correlation we saw in this study is compelling," Lieu says.

Current studies are exploring the use of drugs that block more blood-vessel-growth-promoting factors than VEGF-A. For example, Lieu points to the example of aflibercept (Zaltrap), which was given FDA approval in August, 2013 for the treatment of metastatic colorectal cancer, along with the chemotherapy regimen known as FOLFIRI. The drug inhibits placental growth factor along with VEGF-A.

"It's an attractive strategy, and also proof of concept that by targeting not only the primary mechanism of tumor growth but also one or more of these 'workarounds,' this drug or other future drugs could stall growth longer than blocking any one of these growth factors, individually," Lieu says.

Lieu points out that in addition to targeting these additional growth factors, the fact that spikes in VEGF-C and placental growth factor presage tumor progression could give doctors and researchers a clue that bevacizumab has lost its efficacy. Though more work is needed, Lieu can imagine using spikes in VEGF-C or prenatal growth factor to recommend evaluating new treatment options.


Story Source:

The above story is based on materials provided by University of Colorado Cancer Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Christopher H. Lieu, Hai Tran, Zhi-Qin Jiang, Muling Mao, Michael J. Overman, E. Lin, Cathy Eng, Jeffrey Morris, Lee Ellis, John V. Heymach, Scott Kopetz. The Association of Alternate VEGF Ligands with Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer. PLoS ONE, 2013; 8 (10): e77117 DOI: 10.1371/journal.pone.0077117

Cite This Page:

University of Colorado Cancer Center. "Researchers detail possible resistance mechanisms of colorectal cancer to bevacizumab (avastin)." ScienceDaily. ScienceDaily, 28 October 2013. <www.sciencedaily.com/releases/2013/10/131028184801.htm>.
University of Colorado Cancer Center. (2013, October 28). Researchers detail possible resistance mechanisms of colorectal cancer to bevacizumab (avastin). ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2013/10/131028184801.htm
University of Colorado Cancer Center. "Researchers detail possible resistance mechanisms of colorectal cancer to bevacizumab (avastin)." ScienceDaily. www.sciencedaily.com/releases/2013/10/131028184801.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. 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