Featured Research

from universities, journals, and other organizations

Blood-pressure drug may help improve cancer treatment

Date:
October 1, 2013
Source:
Massachusetts General Hospital
Summary:
Use of existing, well-established hypertension drugs could improve the outcome of cancer chemotherapy by opening up collapsed blood vessels in solid tumors.

Top image: Before treatment with the angiotensin inhibitor losartan, stresses within a tumor caused by the buildup of collagen (blue) compress blood vessels and restrict blood flow (green). Bottom image: After losartan treatment, blood vessels open up, restoring the blood flow required for effective chemotherapy. (Vikash Chauhan, PhD, Steele Lab for Tumor Biology, Massachusetts General Hospital)
Credit: Vikash Chauhan, Ph.D., Steele Lab for Tumor Biology, Massachusetts General Hospital

Use of existing, well-established hypertension drugs could improve the outcome of cancer chemotherapy by opening up collapsed blood vessels in solid tumors. In their report in the online journal Nature Communications, Massachusetts General Hospital (MGH) investigators describe how the angiotensin inhibitor losartan improved the delivery of chemotherapy drugs and oxygen throughout tumors by increasing blood flow in mouse models of breast and pancreatic cancer. A clinical trial based on the findings of this study is now underway.

"Angiotensin inhibitors are safe blood pressure medications that have been used for over a decade in patients and could be repurposed for cancer treatment," explains Rakesh K. Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and senior author of the study. "Unlike anti-angiogenesis drugs, which improve tumor blood flow by repairing the abnormal structure of tumor blood vessels, angiotensin inhibitors open up those vessels by releasing physical forces that are applied to tumor blood vessels when the gel-like matrix surrounding them expands with tumor growth."

Focusing on how the physical and physiological properties of tumors can inhibit cancer therapies, Jain's team previously found that losartan improves the distribution within tumors of relatively large molecules called nanomedicines by inhibiting the formation of collagen, a primary constituent of the extracellular matrix. The current study looked at whether losartan and other drugs that block the action of angiotensin -- a hormone with many functions in the body -- could release the elevated forces within tumors that compress and collapse internal blood vessels. These stresses are exerted when cancer-associated fibroblasts (CAFs) -- specialized cells in the tumor microenvironment -- proliferate and produce increased levels of both collagen and a gel-like substance called hyaluronan.

The team's experiments in several mouse models showed that both collagen and hyaluronan are involved in the compression of blood vessels within tumors and that losartan inhibited production of both molecules by CAFs through reducing the activation and overall density of these cells. Compared with drugs called ACE inhibitors, which block angiotensin signaling in a different way, losartan and drugs of its class -- termed angiotensin receptor blockers -- appeared better at reducing compression within tumors. In models of breast and pancreatic cancer, treatment with losartan alone had little effect on tumor growth, but combining losartan with standard chemotherapy drugs delayed the growth of tumors and extended survival.

"Increasing tumor blood flow in the absence of anti-cancer drugs might actually accelerate tumor growth, but we believe that combining increased blood flow with chemotherapy, radiation therapy or immunotherapy will have beneficial results," explains Jain, the Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School. "Based on these findings in animal models, our colleagues at the MGH Cancer Center have initiated a clinical trial to test whether losartan can improve treatment outcomes in pancreatic cancer." Information on this trial is available at http://clinicaltrials.gov/show/NCT01821729.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Vikash P. Chauhan, John D. Martin, Hao Liu, Delphine A. Lacorre, Saloni R. Jain, Sergey V. Kozin, Triantafyllos Stylianopoulos, Ahmed S. Mousa, Xiaoxing Han, Pichet Adstamongkonkul, Zoran Popović, Peigen Huang, Moungi G. Bawendi, Yves Boucher, Rakesh K. Jain. Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nature Communications, 2013; 4 DOI: 10.1038/ncomms3516

Cite This Page:

Massachusetts General Hospital. "Blood-pressure drug may help improve cancer treatment." ScienceDaily. ScienceDaily, 1 October 2013. <www.sciencedaily.com/releases/2013/10/131001115646.htm>.
Massachusetts General Hospital. (2013, October 1). Blood-pressure drug may help improve cancer treatment. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2013/10/131001115646.htm
Massachusetts General Hospital. "Blood-pressure drug may help improve cancer treatment." ScienceDaily. www.sciencedaily.com/releases/2013/10/131001115646.htm (accessed September 19, 2014).

Share This



More Health & Medicine News

Friday, September 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
How The 'Angelina Jolie Effect' Increased Cancer Screenings

How The 'Angelina Jolie Effect' Increased Cancer Screenings

Newsy (Sep. 19, 2014) Angelina's Jolie's decision to undergo a preventative mastectomy in 2013 inspired many women to seek early screenings for the disease. Video provided by Newsy
Powered by NewsLook.com
The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. Video provided by Reuters
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:
from the past week

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