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:6/25/2017)... ... June 25, 2017 , ... CareSet Labs released the Root NPI ... This is a new, greatly improved version of the Doctor Referral teaming dataset commonly ... Fred Trotter and subsequently called the the “Doctor Referral Dataset” as released by Medicare ...
(Date:6/24/2017)... ... June 24, 2017 , ... Genes Advice, a new company ... Florida and Texas doctors' offices and clinics. This breakthrough testing is part of ... recognizes the role genes play in determining an individual's tolerance of and reaction ...
(Date:6/24/2017)... ... , ... The weather is heating up and the days are getting longer, ... aware that the summer months provide more than warmer temperatures that are perfect for ... negatively affected from direct exposure to the sun. When it comes to the security ...
(Date:6/23/2017)... ... June 23, 2017 , ... "The Better Care Reconciliation Act ... harm to people with all chronic conditions, including mental illnesses, while increasing the ... the Affordable Care Act (ACA) requirement that insurers cover pre-existing conditions, it does ...
(Date:6/23/2017)... ... 24, 2017 , ... Studies show evidence that carotenoids and antioxidants derived either ... in these patients. , But how often do ophthalmologists and optometrists in Sweden recommend ... risk of or with early symptoms of AMD? A study published recently ...
Breaking Medicine News(10 mins):
(Date:6/9/2017)... Calif. , June 9, 2017 AirXpanders, ... company focused on the design, manufacture, sale and distribution ... market on the progress of its commercial roll-out in ... now available in more than one hundred (100) medical ... AeroForm offers a needle-free alternative for women ...
(Date:6/7/2017)... , June 7, 2017 Endo International plc ... 7, 2017, the Hon. Joseph R. Goodwin , ... West Virginia , entered a case ... Pelvic Repair System Products Liability Litigation (the "MDL") that ... cases to provide expert disclosures on specific causation within ...
(Date:6/3/2017)... 3, 2017  Eli Lilly and Company (NYSE: ... from the Phase 3 MONARCH 2 study showed ... inhibitor, in combination with fulvestrant, significantly improved progression-free ... in women with hormone-receptor-positive (HR+), human epidermal growth ... have relapsed or progressed after endocrine therapy (median ...
Breaking Medicine Technology: