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:10/13/2017)... ... 13, 2017 , ... Many families have long-term insurance that covers care for ... a waiver for care if the client has a cognitive impairment diagnosis. , ... care, is often waived, so the benefits from their insurance start immediately,” said Mechell ...
(Date:10/13/2017)... ... October 13, 2017 , ... Talented host, actor Rob Lowe, ... in a new episode of "Success Files," which is an award-winning educational program ... investigates each subject in-depth with passion and integrity. , Sciatica occurs when the ...
(Date:10/12/2017)... , ... October 12, 2017 , ... ... now treating sleep apnea using cutting-edge Oventus O2Vent technology. As many ... sleep disorder characterized by frequent cessation in breathing. Oral appliances can offer significant ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... in post-acute health care, have expanded their existing home health joint venture through ... AccentCare has been operating a joint venture home health company with Asante, delivering ...
(Date:10/12/2017)... ... October 12, 2017 , ... On Saturday, October 21, the Health & Wellness ... Moonlight to raise money for the American Heart Association Heart Walk. Teams of up ... work together to keep their treadmills moving for 5 hours. Treadmills will start at ...
Breaking Medicine News(10 mins):
(Date:10/5/2017)... , Oct. 5, 2017  In response ... of Oral and Maxillofacial Surgeons (AAOMS) released prescribing ... – to be used as a first-line therapy ... Recognizing the ... AAOMS White Paper "Opioid Prescribing: Acute and Postoperative ...
(Date:10/4/2017)... 4, 2017 OBP Medical , ... medical devices, today announced regulatory approval from ... (or Agência Nacional de Vigilância Sanitária (ANVISA)) to ... surgical retractor with integrated LED light source and ... and exposure of a tissue pocket or cavity ...
(Date:10/2/2017)... , Oct. 2, 2017  AllianceRx Walgreens Prime, ... formed by Walgreens and pharmacy benefit manager Prime Therapeutics ... new brand, which included the unveiling of new signage ... , as well as at a few other company-owned ... new brand to patients, some of whom will begin ...
Breaking Medicine Technology: