Navigation Links
New way to target - and kill - proliferating tumors

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
University of California - San Diego

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:
Related Image:
New way to target - and kill - proliferating tumors
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... Comfort ... the American Cancer Society and the Road To Recovery® program to drive cancer patients ... seniors and other adults to ensure the highest quality of life and ongoing independence. ...
(Date:6/24/2016)... ... June 24, 2016 , ... People across the U.S. ... magazine’s Code Talker Award, an essay contest in which patients and their families pay ... be presented at the 2016 National Society of Genetic Counselors (NSGC) Annual Education Conference ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Haute Beauty Network, affiliated ... Weintraub as a prominent plastic surgeon and the network’s newest partner. , ... most handsome men, look naturally attractive. Plastic surgery should be invisible.” He stands ...
(Date:6/24/2016)... ... June 24, 2016 , ... Strategic Capital Partners, ... economy by obtaining investment capital for emerging technology companies. SCP has delivered ... already resulted in more than a million dollars of capital investment for five ...
(Date:6/24/2016)... ... June 24, 2016 , ... Venture Construction Group ... Tournament held on June 20th at the Woodmont Country Club at 1201 Rockville ... an organization dedicated to helping service members that have been wounded in battle and ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016 Research and ... Global Market - Forecast to 2022" report to their ... treatment method for the patients with kidney failure, it replaces ... fluid from the patient,s blood and thus the treatment helps ... and chloride in balance. Increasing number of ...
(Date:6/23/2016)... , June 23, 2016 ... "Pharmaceutical Excipients Market by Type (Organic Chemical (Sugar, ... Formulation (Oral, Topical, Coating, Parenteral) - Global Forecast to ... The global pharmaceutical excipients market ... at a CAGR of 6.1% in the forecast period ...
(Date:6/23/2016)... -- Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that ... PCT (procalcitonin) assay as a dedicated testing solution for ... clearance, Roche is the first IVD company in the ... risk assessment and management. PCT is a ... in blood can aid clinicians in assessing the risk ...
Breaking Medicine Technology: