Navigation Links
New way to target - and kill - proliferating tumors
Date:11/13/2011

Researchers at the University of California, San Diego School of Medicine and the UC San Diego Moores Cancer Center have identified a new drug discovery approach enabling the destruction of the most highly proliferative tumors. The discovery, published in the Nov. 13 online issue of the journal Nature Medicine, points to an effective, alternative method for killing fast-growing cancer cells without causing some of the negative effects of current therapies.

The scientists, led by David A. Cheresh, PhD, professor of pathology and associate director for translational research at the Moores Cancer Center, used an innovative chemical and biological approach to design a new class of drugs that arrests division in virtually all tumor cells by binding to and altering the structure of an enzyme called RAF.

RAF has been long-studied, but its role in cell division critical to cell proliferation and tumor growth was a surprise. "By designing a new class of drugs that changes the shape of RAF, we were able to reveal this previously undiscovered role for RAF in a wide range of highly proliferative tumors," Cheresh said.

Current cancer drugs that target enzymes like RAF are generally designed to interact with the active site of the enzyme. Unfortunately, these drugs often lack specificity, Cheresh said. "They hit many different targets, meaning they can produce undesired side effects and induce dose-limiting toxicity." More of a concern is that tumor cells often develop resistance to this class of drugs rendering them inactive against the cancer.

Cheresh and colleagues pursued development of a new class of RAF inhibitors that do not bind to the active site of the enzyme and so avoid the limitations of current drugs. Instead, this new class, called allosteric inhibitors, changes the shape of the target enzyme and in doing so, renders it inactive. The specific drug tested, known as KG5, singles out RAF in proliferating cells, but ignores normal or resting cells. In affected tumor cells, RAF is unable to associate with the mitotic apparatus to direct cell division, resulting in cell cycle arrest leading to apoptosis or programmed cell death. KG5 in a similar manner effectively interferes with proliferating blood vessels, a process called angiogenesis.

"It's an unusual discovery, one that really challenges current dogma," said Cheresh. "Before this drug was designed, we had no idea RAF could promote tumor cell cycle progression. This may be only one example of how, by designing drugs that avoid the active site of an enzyme, we can identify new and unexpected ways to disrupt the growth of tumors. In essence, we are attacking an important enzyme in a whole new way and thereby discovering new things this enzyme was intended for."

KG5 produced similar results in tests on cancer cell lines, in animal models and in tissue biopsies from human cancer patients. The research team has since developed variants of KG5 that are 100-fold more powerful than the original drug. They hope one of these more powerful compounds will soon enter clinical trials at Moores Cancer Center.

The new RAF targeted compounds are being developed by Amitech Therapeutic Solutions, Inc a start-up company in San Diego.


'/>"/>
Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert  

Related medicine news :

1. Marker of Ewing sarcoma: Potential new drug target?
2. Dana-Farber and Sanford-Burnham Institute license flu-targeting antibodies to Genentech and Roche
3. New therapeutic target for most common solid cancer in childhood?
4. Fans Spread the Love on Target Facebook Page and Help Donate $1 Million to Five Charities
5. New Multivitamins Target Concern Over China's Quality Problems
6. Targeted delivery of losartan reduces liver inflammation and scarring
7. New Study: Improved Immune System with Gene-Eden, a Natural Antiviral Supplement that Targets Chronic Viruses
8. TV Ads Target House Members Who Voted for Obamacare
9. Targeting leukemia cells gene addiction presents new strategy for treatment
10. Hot Pepper Itch Remedy Targets Kidney Disease Patients Suffering From Chronic Pruritus
11. Americans for Responsible Health Care Launch Radio Ads Targeting Seven Democrats, Warning The People Are Watching...
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New way to target - and kill - proliferating tumors
(Date:2/11/2016)... ... 11, 2016 , ... "What holds you back from ... a question as a challenge for his readers to examine the full scale ... (published by Partridge Singapore), Clarke explores the subject with more depth, revealing time-honored ...
(Date:2/11/2016)... , ... February 11, 2016 , ... ... of a master charity program created to assist the people of their local ... closely with nonprofit organizations and community leaders. Their hope is to bring awareness ...
(Date:2/11/2016)... ... February 11, 2016 , ... Talix today announced ... , will be presenting at the 2016 HIMSS Annual Conference & Exhibition, taking ... During his session, “ Coding for Care: Using Data Analytics for Risk Adjustment ...
(Date:2/11/2016)... ... 11, 2016 , ... The annual list showcases the 20 Most Promising SharePoint ... dedication and commitment to the SharePoint ecosystem. A panel of experts and members ... is to recognize and promote technology entrepreneurship. , The survey was made at ...
(Date:2/11/2016)... D.C. (PRWEB) , ... February 11, 2016 , ... ... will be exhibiting at the American Academy of Dermatology Annual Meeting at the ... USA's goal is to raise awareness for both the condition of hyperhidrosis (excessive ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... DIEGO , Feb. 11, 2016 ... groundbreaking cell-isolation method that opens the door to ... until now have been impossible to isolate with ... to isolate specific tumor types in various stages ... genetic variants of these cells that are clinically ...
(Date:2/11/2016)... , Feb. 11, 2016  AcelRx Pharmaceuticals, Inc. ... presentation will be made at the 38th annual ... Wound Care Symposium, which is being held February 14-18, ... conference covers the latest advancements in wound healing, burn ... American Burn Association, Australian-New Zealand Burns Association, Academy of ...
(Date:2/11/2016)... 11, 2016  Ampio Pharmaceuticals, Inc. (NYSE MKT: AMPE) ... into a Controlled Equity Offering SM Sales Agreement ... Michael Macaluso , Chairman and CEO, stated "During our ... not currently raising money and that we have enough ... and still complete all of our current objectives and ...
Breaking Medicine Technology: