Featured Research

from universities, journals, and other organizations

Cancer Therapy: A Role For MAPK Inhibitors Combined With MTORC1 Inhibitors

Date:
August 21, 2008
Source:
Beth Israel Deaconess Medical Center
Summary:
Researchers identify a previously unrecognized problem faced by mTOR inhibitors when it comes to attacking cancers. Nearly a decade ago, while it was being tested as an immunosuppressive agent to prevent organ rejection in transplant patients, the drug rapamycin was also discovered to have anti-tumor properties. Since then, several rapamycin analogs known as mTOR (mammalian target of rapamycin) inhibitors have been tested in clinical trials for the treatment of various types of cancer.

Nearly a decade ago, while it was being tested as an immunosuppressive agent to prevent organ rejection in transplant patients, the drug rapamycin was also discovered to have anti-tumor properties. Since then, several rapamycin analogs known as mTOR (mammalian target of rapamycin) inhibitors have been tested in clinical trials for the treatment of various types of cancer.

But despite promising early results, mTOR inhibitors have proven less successful than originally expected.

Now research led by scientists at Beth Israel Deaconess Medical Center (BIDMC) identifies a previously unrecognized problem faced by these agents when it comes to attacking cancers. Reported in the August 21 advance on-line issue of The Journal of Clinical Investigation (JCI), the new findings show that at the same time that rapamycin analogs are halting tumor growth by inhibiting the mTOR protein complex 1 (mTORC1), they are activating the MAPK (mitogen-activated protein kinase) pathway -- thereby encouraging cancer cell survival.

"Anticancer research is aimed at understanding the molecular pathways that can be selectively targeted to halt tumor growth," explains senior author Pier Paolo Pandolfi, MD, PhD, Director of Basic Research of the Cancer Center at BIDMC and Professor of Medicine at Harvard Medical School. "We know that the mTOR pathway is activated in many cancers, and therefore, is a good target for fighting a wide array of tumors."

The mTOR pathway controls cell growth and angiogenesis through a series of mechanisms that integrate signaling from nutrients and other growth-promoting pathways. Activation of mTOR, therefore, promotes the proliferation of tumor cells, while inhibition of mTOR counters this action. However, because the mTOR signaling pathway is extremely complex, scientists have focused their efforts on identifying other agents that could be successfully combined with mTOR inhibitors to halt cancer growth.

The new findings shine a light on MAPK, a signaling pathway also known for its role in sensing growth factors to promote cell survival and proliferation.

"We analyzed tissue from human biopsies, as well as cancer cell lines and genetically engineered mouse models of cancer," explains the study's first author Arkaitz Carracedo, PhD, a postdoctoral fellow in the Pandolfi laboratory. "These experiments all pointed to the MAPK pathway."

From there, Carracedo and his coauthors went on to test a group of MAPK inhibitor agents to find out if, in combination with mTOR inhibitors, the agents would act to counter any pro-survival activity. And they did.

"This study inserts a new piece of information into the puzzle of the effects of mTORC1 inhibitors in cell signaling," says Pandolfi. "Furthermore, because there are inhibitors of MAPK pathway already approved for the treatment of cancer, it provides us with the rationale for using combinations of mTORC1 and MAPK inhibitors in attacking tumors, thereby offering cancer patients another treatment option with immediate applicability."

In addition to Pandolfi and Carracedo, study coauthors include BIDMC investigators Leonardo Salmena, Andrea Alimonti, Ainara Egia, Atsuo Sasaki, Antonella Papa, Caterina Nardella and Lewis Cantley; Memorial Sloan-Kettering Cancer Center investigator Julie Teruya-Feldstein in New York; Li Ma currently in the Whitehead Institute for Biomedical Research, Cambridge; George Thomas and Sara Kozma of the University of Cincinnati; and Federico Rojo and Jose Baselga from Vall d'Hebron University Hospital in Barcelona, Spain.

This work was supported, in part, by grants from the National Institutes of Health.


Story Source:

The above story is based on materials provided by Beth Israel Deaconess Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Beth Israel Deaconess Medical Center. "Cancer Therapy: A Role For MAPK Inhibitors Combined With MTORC1 Inhibitors." ScienceDaily. ScienceDaily, 21 August 2008. <www.sciencedaily.com/releases/2008/08/080821194721.htm>.
Beth Israel Deaconess Medical Center. (2008, August 21). Cancer Therapy: A Role For MAPK Inhibitors Combined With MTORC1 Inhibitors. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2008/08/080821194721.htm
Beth Israel Deaconess Medical Center. "Cancer Therapy: A Role For MAPK Inhibitors Combined With MTORC1 Inhibitors." ScienceDaily. www.sciencedaily.com/releases/2008/08/080821194721.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) — A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
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