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:1/16/2017)... (PRWEB) , ... January 17, 2017 , ... Recently, patients ... in Southwest Michigan, joined other volunteers and organizations in support of the annual Binder ... children and families dressed up in colorful costumes of all designs coming out to ...
(Date:1/16/2017)... Elk Grove Village, IL (PRWEB) , ... January ... ... protection and personal audio products, will demonstrate their groundbreaking GunSport•PRO® and EB15•LE® electronic ... Expo and Convention Center in Las Vegas, Booth #2809. The SHOT Show is ...
(Date:1/16/2017)... ... January 16, 2017 , ... Houston ... Center, is currently offering complimentary consultations and financing for orthodontics for a limited ... bite irregularities and learn about their orthodontic options. Walk-in, late-evening, Saturday, and same-day ...
(Date:1/16/2017)... ... January 16, 2017 , ... Specialty Technical Publishers (STP) ... Audit Protocol Consortium (IAPC) EHS audit protocol for Singapore . Leading companies ... their EHS regulatory obligations and rapidly collect, share, archive, and export audit findings ...
(Date:1/16/2017)... Grants Pass, OR (PRWEB) , ... January 16, ... ... Kent Heckenlively, author, editor, attorney, science teacher, http://www.ageofautism.com/legal , Sharon Kleyne, ... and attorney Kent Heckenlively to her nationally syndicated radio program, The Sharon Kleyne ...
Breaking Medicine News(10 mins):
(Date:1/17/2017)... -- Immune Pharmaceuticals (NASDAQ: IMNP ) ("Immune"), ... will hold a Satellite Symposium on February 20th, 2017 at ... Munich, Germany . The ... for the maintenance of remission in AML with Ceplene" ... 2017 from 12:45 – 13:45 CET in Lecture Hall ...
(Date:1/17/2017)... , Jan 17, 2017 Research and Markets ... 2016-2020" report to their offering. ... The global laparotomy sponges market to grow ... Global Laparotomy Sponges Market 2016-2020, has been prepared based ... report covers the market landscape and its growth prospects over the ...
(Date:1/17/2017)... Minn. , Jan. 17, 2017  ANI ... today announced the appointment of Karen Quinn Ph.D ... 17, 2017.  Karen Quinn ... of leadership experience in Global Regulatory Affairs, specifically ... active pharmaceutical ingredients.  Dr. Quinn worked most recently ...
Breaking Medicine Technology: