Navigation Links
New idea for targeting the common cancer protein KRAS
Date:10/20/2013

BOSTON Patients with cancers driven by the protein KRAS, which are particularly hard to treat, may benefit from small molecules that attach to and disrupt the function of a KRAS-containing protein complex, according to results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19-23.

Mutant forms of the protein KRAS are found in approximately 30 percent of all cancers. They are responsible for many of the hallmarks of these cancers, and KRAS is, therefore, considered an important therapeutic target. However, attempts to develop clinically useful KRAS-targeted drugs have been unsuccessful.

"KRAS is a molecular switch," said Michael Burns, a doctor of medicine and doctor of philosophy candidate at Vanderbilt School of Medicine in Nashville, Tenn. "In the 'on' state it transmits signals that drive cell growth and survival. In many cancers, KRAS is permanently in the on state, and it is a highly validated therapeutic target.

"KRAS switches from off to on most efficiently when it is attached to a protein called SOS," explained Burns. "Each SOS protein attaches to two KRAS proteins, and we have identified a number of small molecules that bind to a particular part of SOS when it is in a complex with two KRAS proteins. These small molecules disrupt the function of the complex, ultimately causing inhibition of the signaling pathways downstream of KRAS that drive cell growth and survival. Although our data were generated in biochemical assays and cell lines, they suggest a potential way to therapeutically target KRAS, which has not been possible to date."

KRAS switches from off to on during a process called guanine nucleotide exchange, and SOS increases the rate at which this process occurs. Burns and colleagues hypothesized that small molecules that blocked SOS-mediated guanine nucleotide exchange would prevent KRAS switching on and, therefore, inhibit the signaling pathways downstream of KRAS that drive cell growth and survival.

Instead, they found that a number of small molecules that attached to a special pocket in a region of SOS called the CDC25 domain and increased SOS-mediated guanine nucleotide exchange actually inhibited two of the major signaling pathways downstream of KRAS: the MAPK and PI3K signaling pathways.

The researchers are actively investigating why small molecules that increased SOS-mediated guanine nucleotide exchange in biochemical assays blocked signaling downstream of KRAS in cell lines. They are also working to optimize the small molecules before they conduct studies in preclinical models of cancer.


'/>"/>

Contact: Lauren Riley
lauren.riley@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. GUARDaHEART Hosts an Unforgettable Evening in Celebration of World Heart Day “Targeting Heart Disease”
2. Targeting memory T-cells in Type 1 diabetes
3. Targeting aggressive prostate cancer
4. Nanodrug targeting breast cancer cells from the inside adds weapon: Immune system attack
5. Cancer research brief: Targeting pancreatic cancer drug resistance
6. Targeting errant immune system enzyme kills myelodysplastic cells
7. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Offer Improved hCG Diet Plans Capable of Targeting Stubborn Belly Fat Now Linked With Decreased Bone Density
8. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Now Offer New Weight Loss Diets that Educate Patients, Targeting Weight Gained During Childhood and Adolescence
9. Overcoming resistance to anti-cancer drugs by targeting cell powerhouses
10. Study Shows Dual Targeting of HER2 and HR-positive Metastatic Breast Cancer Improves Survival Rates
11. Drugs targeting blood vessels may be candidates for treating Alzheimers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/2/2016)... ... 02, 2016 , ... ‘Tis the season for giving! Today, 20 creative teams ... Family Partnership and the Drug Enforcement Administration as part of the National Red Ribbon ... winning schools who decorated their campuses with this year’s Red Ribbon Week theme: “YOLO. ...
(Date:11/30/2016)... ... November 30, 2016 , ... "I hate when the mixture of saliva ... teeth," said an inventor from Bridgewater, N.J. "I thought that there had to be ... , He developed the patent-pending DEFLECTOR to prevent saliva and toothpaste from running down ...
(Date:11/30/2016)... ... November 30, 2016 , ... Center For Discovery, a ... opening of a new residential mental health treatment program in Chino Hills, California.  The ... as severe anxiety, depression, bi-polar disorder, and other related issues. , Center For ...
(Date:11/30/2016)... ... November 30, 2016 , ... The ... community that the FDA Binding Guidance goes into effect next month. Sponsors whose ... in the FDA Data Standards Catalog. The current FDA Data Standards Catalog specifies ...
(Date:11/30/2016)... ... , ... BrightStar Care of Wellington , a home care agency that ... 2016 Provider and Employer of Choice by Home Care Pulse. The Best of Home ... with the highest quality receive the Best of Home Care Award from Home Care ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... 2, 2016 Research and Markets has announced ... Growth and Demand Forecast to 2022" report to their offering. ... , , ... in 2015, and it is expected to grow at a CAGR of ... to witness faster growth during the forecast period, a CAGR of 8.8% ...
(Date:12/2/2016)... In the first ever attempt to include ... from C. sativa, the Hebrew University in Jerusalem, the ... II , the Universita` del Piemonte Orientale and Phytoplant ... and unified inventory of phytocannabinoids of different botanical origin. ... remarkable chemical and structural diversity of phytocannabinoids. As a ...
(Date:12/2/2016)... Dec. 2, 2016  Maxor National Pharmacy Services, LLC ("Maxor"), ... Specialties, Inc. ("PSI").  The combination of Texas ... -based PSI bring together both company,s clinical expertise and ... payers an industry-leading specialty pharmacy. About Maxor ... , , ...
Breaking Medicine Technology: