Featured Research

from universities, journals, and other organizations

New drug combinations may benefit patients with pancreatic cancer

Date:
October 21, 2013
Source:
American Association for Cancer Research
Summary:
Two drug combinations that simultaneously block two major signaling pathways downstream of the protein KRAS, which is aberrantly active in most pancreatic cancers, may provide a new treatment option for patients with this disease, according to preclinical results.

Two drug combinations that simultaneously block two major signaling pathways downstream of the protein KRAS, which is aberrantly active in most pancreatic cancers, may provide a new treatment option for patients with this disease, according to preclinical results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19-23.

Pancreatic cancer is one of the deadliest types of cancer, with a five-year survival rate of just 6 percent. Most pancreatic cancers harbor mutations in the KRAS gene. Because these mutations drive many of the cancerous characteristics of pancreatic cancer cells, the KRAS protein is a prime therapeutic target. However, efforts to develop clinically useful drugs that block KRAS activity have been unsuccessful.

"KRAS has been a daunting therapeutic target," said Barry Nelkin, Ph.D., professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Md. "By combining drugs that simultaneously block two of the major signaling pathways triggered by KRAS, we have found a way to indirectly target this challenging protein.

"Our preclinical results were so positive that we have initiated a phase I clinical trial to evaluate one of the drug combinations, dinaciclib plus MK2206, in patients with pancreatic cancer."

In prior studies, Nelkin and colleagues found that an investigational drug called dinaciclib had antitumor effects in mouse models of pancreatic cancer.

"Dinaciclib blocks the activity of a protein called CDK5, which is a key part of one of the signaling pathways that KRAS uses to exert its cancer-driving effects, the Ral pathway," explained Nelkin. "We wanted to investigate whether combining dinaciclib with a second drug that blocks one of the other signaling pathways triggered by KRAS would have even greater antitumor effects."

To conduct the study, Nelkin and colleagues used models of pancreatic cancer that closely resembled the human disease: They placed tiny pieces of human pancreatic tumors in the pancreata of mice and let them grow to about the size of a pea before beginning treatment.

The combination of dinaciclib and MK2206, which blocks the PI3K/AKT pathway triggered by KRAS, substantially inhibited tumor growth and reduced tumor spread to other parts of the body, a process called metastasis, compared with either drug alone. Further, when compared with no treatment, this drug combination reduced tumor growth by 90 percent, and in three of the 14 mice, no human pancreatic tumor tissue could be detected at the end of the experiment, indicating that there had been a complete response to the treatment.

The second drug combination tested -- dinaciclib and SCH772984, which blocks the RAF/MEK/ERK pathway triggered by KRAS -- also substantially inhibited tumor growth and reduced the number of metastases. It did not, however, lead to any complete responses.

The researchers are planning to investigate whether the drug combinations they used in this study can be further combined with current treatments for pancreatic cancer and if they can identify markers that might predict whether a given pancreatic tumor will respond to the drug combinations.


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 drug combinations may benefit patients with pancreatic cancer." ScienceDaily. ScienceDaily, 21 October 2013. <www.sciencedaily.com/releases/2013/10/131021095016.htm>.
American Association for Cancer Research. (2013, October 21). New drug combinations may benefit patients with pancreatic cancer. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2013/10/131021095016.htm
American Association for Cancer Research. "New drug combinations may benefit patients with pancreatic cancer." ScienceDaily. www.sciencedaily.com/releases/2013/10/131021095016.htm (accessed September 21, 2014).

Share This



More Health & Medicine News

Sunday, September 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
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

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