Navigation Links
Ganetespib showed activity in KRAS-mutant NSCLC as monotherapy and in combinations
Date:1/10/2012

SAN DIEGO The investigational drug ganetespib, a synthetic second-generation Hsp90 inhibitor, slowed the growth of cancer cells taken from non-small cell lung cancer tumors with a mutation in the KRAS gene. The drug was even more active when combined with traditional lung cancer treatments and other investigational targeted therapies, according to preclinical study data.

David A. Proia, Ph.D., and Jaime Acquaviva, Ph.D., scientists at Synta Pharmaceuticals Corp., presented the data at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine, held Jan. 8-11, 2012.

Currently, patients with non-small cell lung cancer (NSCLC) with KRAS mutations have no effective treatment strategy. A phase 2 trial showed tumor shrinkage in more than 60 percent of patients with KRAS-mutant NSCLC at eight weeks after treatment with ganetespib administered once weekly as a monotherapy, indicating the drug's potential effectiveness, according to Proia.

He and his colleagues examined whether ganetespib was effective against several different cell lines of KRAS-mutant NSCLC and confirmed it was effective in 15 different cell lines. They then sought to determine which combination treatments would enhance the activity of ganetespib in this cancer type.

First, the researchers combined ganetespib with several standard-of-care chemotherapies currently available in the clinic for KRAS-mutant NSCLC tumor samples. They found that the combination of ganetespib with alkylating agents, antimitotics and topoisomerase inhibitors resulted in an increased cell death of 1.4-, 1.5- and 2.6-fold, respectively, compared with ganetespib alone.

"We saw great activity with, for example, docetaxel and [ganetespib]," Proia said. "What we are doing now is conducting a large phase 2b/phase 3 trial with docetaxel and [ganetespib] in NSCLC patients. Activity in the KRAS-mutant subpopulation is a coprimary endpoint in this trial."

The researchers also tested ganetespib in combination with two therapies that target pathways known to be involved in NSCLC: a MEK inhibitor or a PI3K/mTOR inhibitor. Results in tumor samples revealed that combining ganetespib with either therapy was also more active in slowing tumor growth compared with ganetespib alone.

"Not only was ganetespib activity enhanced in combination with traditional chemotherapies, which may be understood in terms of the ability of Hsp90 inhibition to block certain resistance or repair mechanisms, but activity was also enhanced in combination with a number of targeted therapies for which recent work has shown very interesting complementary inhibition of signaling pathways," Proia said.

Finally, the researchers further validated their results by combining ganetespib with the PI3K/mTOR inhibitor in mice with KRAS-mutant NSCLC. Both drugs alone promoted tumor shrinkage, but the combination resulted in a greater inhibition of tumor growth.

If further validated, this research could open up avenues for future treatment options for patients with KRAS-mutant NSCLC.


'/>"/>
Contact: Jeremy Moore
Jeremy.Moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Data on Vivitrol for opioid dependence showed sustained efficacy over 18 months
2. Phone app providing real-time statistics on physical activity around the world
3. Neuroscientists reveal new links that regulate brain electrical activity
4. Legislating to promote healthy eating and physical activity
5. Obesity and physical inactivity poses arthritis risk, especially for women
6. After a fight with a partner, brain activity predicts emotional resiliency
7. Why do sexually experienced girls resume sexual activity after abstinence?
8. Siblings of Kids With Autism May Be Prone to Hyperactivity
9. Optovue Announces Formation of the EYE-GIVE Foundation for World-Wide Eye Care Philanthropy Activity
10. Pollen.com Reports Five U.S. Cities with Highest Pollen Activity -- Total Prescriptions for Allergy Medications 3.7% Higher than Last Year
11. Language dysfunction in children may be due to epileptic brain activity
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... ... April 29, 2016 , ... On Tuesday, April 26, 2016 members of the ... signature of Gov. Nathan Deal on SB 258, the “Rural Health Care Relief” Bill. ... a 70% tax credit to individuals and corporations which donate directly to a “rural ...
(Date:4/29/2016)... ... April 29, 2016 , ... Coast Dental Fort Stewart is celebrating ... new location in the Exchange Furniture Mall at 112 Vilseck Road in Fort Stewart. ... Smart TV. Plus attendees will have the opportunity to meet general dentists Thomas Richards, ...
(Date:4/29/2016)... (PRWEB) , ... April 29, 2016 , ... ... engineer of patented products, announces the Gyrociser, an exercise invention which aids in ... $2 billion," says Scott Cooper, CEO and Creative Director of World Patent Marketing. ...
(Date:4/29/2016)... ... April 29, 2016 , ... Reltok Nasal Products proudly ... for the head and neck/ear, nose and throat specialty, has added the KOTLER NASAL ... KOTLER NASAL AIRWAY™ is a newly patented safety device secured by nasal surgeons ...
(Date:4/29/2016)... ... April 29, 2016 , ... CURE Media Group , ... with cancer, today announced that Lynne Malestic, RN, of Eisenhower Lucy Curci Cancer ... Healer® for Oncology Nursing , which honors nurses who have dedicated their careers ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... 2016  Marking its one year anniversary since ... cancer risk test, Color Genomics announced ... highly impact the most common hereditary cancers affecting ... Test analyzes hereditary cancer risks for breast, colorectal, ... The Color Test is physician ordered and includes ...
(Date:4/28/2016)... 2016 , Net Sales of $1.90 billion ... the prior year period, and an increase of 1.2% on ... EPS for the first quarter were $0.52 reported, a decrease ... an increase of 29.9% over the prior year period ... guidance for 2016 Zimmer Biomet Holdings, Inc. (NYSE ...
(Date:4/28/2016)... , April 28, 2016  ValGenesis, ... Lifecycle Management Solutions (VLMS) today announced that ... services for sufferers of chronic kidney failure ... to manage their corporate validation process. The ... a software solution to manage their validation ...
Breaking Medicine Technology: