Featured Research

from universities, journals, and other organizations

New nanopharmaceutical may help overcome resistance to anticancer drugs

Date:
October 21, 2013
Source:
American Association for Cancer Research
Summary:
The nanopharmaceutical drug CRLX101 is showing promise as a potential new treatment for cancers that develop resistance to antiangiogenic drugs and radiation therapy, according to clinical trial results.

The nanopharmaceutical drug CRLX101 is showing promise as a potential new treatment for cancers that develop resistance to antiangiogenic drugs and radiation therapy, according to clinical trial results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19 -- 23.

Related Articles


Antiangiogenic drugs are anticancer drugs designed to cut off the blood supply that brings tumors the nutrients they need to grow and survive, thereby starving and killing the tumor cells. Over time, however, tumors usually develop resistance to these drugs, often because of the upregulation of a protein called HIF-1 alpha. This protein promotes tumor invasion, metastasis, and cancer stem cell formation, all of which make tumors more aggressive and unmanageable. Antiangiogenesis drugs, as a result, have achieved limited success in the treatment of cancers.

"Reducing or eliminating resistance to antiangiogenic drugs could have meaningful implications for cancer patients. Up until now, HIF-1alpha has been considered impossible to target safely, but CRLX101 may change that," said Scott Eliasof, Ph.D., vice president of Cerulean Pharma Inc., in Cambridge, Mass. "CRLX101 has been shown to inhibit HIF-1alpha, and the clinical data we have obtained to date suggest that it has limited side effects, which may permit it to be effectively combined with other drugs. We believe that CRLX101 may have the potential to manage resistance to antiangiogenic and radiation therapies.

"Based on our preclinical data, we believe CRLX101 may have the potential to have a significant effect on pathological complete response in rectal cancer patients and on overall survival duration in patients with ovarian and kidney cancers," he added.

CRLX101's payload is the toxic anticancer drug, camptothecin, chemically conjugated into nanoparticles of 20-30 nanometers in diameter, using polymeric materials. When CRLX101 is taken up by the tumor cells, preclinical data suggest that the chemical linkers release the payload slowly, ensuring a steady and sustained release of camptothecin over time. This sustained drug release enables durable inhibition of an enzyme called topoisomerase-1, which leads to the inhibition of HIF-1 alpha.

Eliasof and colleagues have initiated four phase II investigator-sponsored clinical trials to test CRLX101 either as a single agent or in combination with an antiangiogenic drug. In one phase Ib/IIa trial, they have recruited nine patients to date with kidney cancer, a cancer that is known to have high levels of HIF-1alpha. All patients had received prior antiangiogenesis therapy with limited success. When treated in this trial with CRLX101 in combination with the antiangiogenic drug bevacizumab, the researchers observed a 33 percent partial response rate in these patients, which is unprecedented according to Eliasof, because the overall response rate is typically 4 percent with bevacizumab alone and 2% with everolimus, the standard of care in this setting. Of note, the maximum tolerated dose of CRLX101 in combination with bevacizumab is the same as the monotherapy dose, suggesting it has low toxicity and higher tolerability. "Nine patients is a small sample size, but we are cautiously optimistic," he said.

An imaging clinical trial in patients with gastric cancers testing CRLX101 revealed more accumulation of the drug in tumors than in the neighboring healthy tissue, suggesting the compound has the potential to be target specific.

Two clinical trials to test CRLX101 as monotherapy in small-cell lung cancer and ovarian cancer are underway. Before year-end, Cerulean plans to launch two additional combination trials, according to Eliasof. The first clinical trial will combine CRLX101 with bevacizumab in ovarian cancer. The second clinical trial will combine CRLX101 with capecitabine and radiation in neoadjuvant rectal cancer.

"We have generated compelling preclinical data showing synergy when CRLX101 is combined with every antiangiogenic agent we have tested to date. Our focus now is on making a difference in the lives of patients in our various clinical trials."


Story Source:

The above story is based on materials provided by American Association for Cancer Research. Note: Materials may be edited for content and length.


Cite This Page:

American Association for Cancer Research. "New nanopharmaceutical may help overcome resistance to anticancer drugs." ScienceDaily. ScienceDaily, 21 October 2013. <www.sciencedaily.com/releases/2013/10/131021095012.htm>.
American Association for Cancer Research. (2013, October 21). New nanopharmaceutical may help overcome resistance to anticancer drugs. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2013/10/131021095012.htm
American Association for Cancer Research. "New nanopharmaceutical may help overcome resistance to anticancer drugs." ScienceDaily. www.sciencedaily.com/releases/2013/10/131021095012.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. 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