(Press-News.org) 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.
###
About the AACR:
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 laboratory, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards to young investigators, and it also funds cutting-edge research projects conducted by senior researchers. The AACR has numerous fruitful collaborations with organizations and foundations in the United States and abroad and functions as the Scientific Partner of Stand Up To Cancer, a charitable initiative that supports groundbreaking research aimed at getting new cancer treatments to patients in an accelerated time frame.
The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care, and Educational Workshops are held for the training of young cancer investigators. The AACR publishes seven major peer-reviewed journals: Cancer Discovery; Cancer Research; Clinical Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Prevention Research. In 2010, AACR journals received 20 percent of the total number of citations given to oncology journals. The AACR also publishes Cancer Today, a magazine for cancer patients, survivors and their caregivers, which provides practical knowledge and new hope for cancer survivors. A major goal of the AACR is to educate the general public and policymakers about the value of cancer research in improving public health, the vital importance of increases in sustained funding for cancer research and biomedical science, and the need for national policies that foster innovation and the acceleration of progress against the 200 diseases we call cancer.
Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association's membership includes more than 3,500 lung cancer specialists in 80 countries.
IASLC members promote the study of etiology, epidemiology, prevention, diagnosis, treatment and all other aspects of lung cancer and thoracic malignancies. IASLC disseminates information about lung cancer to scientists, members of the medical community and the public and uses all available means to eliminate lung cancer as a health threat for individual patients throughout the world. Membership is open to any physician, scientist, nurse or allied health professional interested in lung cancer, including patients, survivors, caregivers and advocates.
IASLC publishes the Journal of Thoracic Oncology, a valuable resource for medical specialists and scientists who focus on the detection, prevention, diagnosis and treatment of lung cancer.
To learn more about IASLC, visit http://iaslc.org
Ganetespib showed activity in KRAS-mutant NSCLC as monotherapy and in combinations
2012-01-11
ELSE PRESS RELEASES FROM THIS DATE:
Precancer markers identified in airway epithelium cells of healthy smokers
2012-01-11
SAN DIEGO -- Smoking may be associated with the development of molecular features of cancer in the large airway epithelium. In the small airway epithelium, molecular cancerization is associated with development of chronic obstructive pulmonary disease, according to recent data.
"We are striving to find the earliest molecular changes that are induced by environmental stressors — in this case, smoking," said Renat Shaykhiev, M.D., Ph.D., assistant professor of genetic medicine at Weill Cornell Medical College, who presented the findings at the AACR-IASLC Joint Conference ...
Preventing mother to child transmission of HIV in Zimbabwe
2012-01-11
Preventing mother to child transmission of HIV in Zimbabwe
In this week's PLoS Medicine, Andrea Ciaranello of Massachusetts General Hospital, Boston, USA and colleagues find, using a simulation model, that implementation of the latest WHO PMTCT (prevention of mother to child transmission of HIV) guidelines must take place in conjunction with improving access to PMTCT programs, increasing retention of women in care, and supporting adherence to drugs, in order to eliminate pediatric HIV in Zimbabwe.
The authors say: "Although PMTCT uptake in low- and middle-income countries ...
Limited use of compulsory licensing of pharmaceuticals to protect public health
2012-01-11
Limited use of compulsory licensing of pharmaceuticals to protect public health
Reed Beall and Randall Kuhn of the University of Denver, USA describe in this week's PLoS Medicine their findings from an analysis of use of compulsory licenses for pharmaceutical products by World Trade Organization members since 1995. Specifically, the authors investigated the impact of the 2001 Doha Declaration on trends in compulsory licensing of pharmaceuticals. They highlight the need for further systematic evaluation of global health agreements.
###Funding: No direct funding was received ...
Long-term consequences of venous thrombosis
2012-01-11
Long-term consequences of venous thrombosis
Linda Flinterman of Leiden University, the Netherlands and colleagues report in this week's PLoS Medicine on the long-term mortality rate for individuals who have experienced a first venous thrombosis or pulmonary embolism. They describe an ongoing elevated risk of death for individuals who had experienced a venous thrombosis or pulmonary embolism as compared to controls, for up to eight years after the event.
The authors say: "To our knowledge, this has been the first study to calculate mortality rates compared with the general ...
How can we improve global access to pain relief?
2012-01-11
Jason Nickerson and Amir Attaran of the University of Ottawa, Canada examine in this week's PLoS Medicine the vast inequities in medical pain relief around the world, arguing that the imbalance has arisen from restrictive drug laws designed to prevent access to illegal substances, and proposing that the global control of licit narcotics be shifted from the International Narcotic Control Board to WHO.
The authors say: "Transferring the public health responsibility for controlled medicines from INCB to WHO would end the impossibly contradictory situation in which INCB ...
Study shows early primate had a transitional lemur-like grooming claw
2012-01-11
GAINESVILLE, Fla. --- Celebrities are channeling a distant relative with what Harper's Bazaar describes as the latest trend in nail fashion for 2012: claws. But this may not be the first time primates traded their nails for claws.
A new study co-authored by a University of Florida researcher examines the first extinct North American primate with a toe bone showing features associated with the presence of both nails and a grooming claw, indicating our primate ancestors may have traded their flat nails for raised claws for functional purposes, much like pop icons Adele ...
Marijuana smoke not as damaging to lungs as cigarette smoke
2012-01-11
BIRMINGHAM, Ala. – Using marijuana carries legal risks, but a new study shows that the consequences of occasionally lighting up do not include long-term loss of lung function, according to a new study by University of Alabama at Birmingham researchers published in the January 11, 2012, issue of the Journal of the American Medical Association.
Marijuana is the most commonly used illicit drug in the United States, according to the National Survey on Drug Use and Health. In 2009, 16.7 million Americans ages 12 and older reported using marijuana at least once in the month ...
How can pediatric HIV be eliminated in Zimbabwe?
2012-01-11
Eliminating new infant HIV infections in Zimbabwe will require not only improved access to antiretroviral medications but also support to help HIV-infected mothers continue taking their medication and safely reduce or eliminate breastfeeding, according to an article in the January issue of PLoS Medicine. Findings of the report from an international research team should help with the planning of expanded programs to prevent mother-to-child HIV transmission in sub-Saharan Africa and other areas with limited health resources.
"Pediatric HIV infection has been nearly eliminated ...
Before they were stars
2012-01-11
The stars we see today weren't always as serene as they appear, floating alone in the dark of night. Most stars, likely including our sun, grew up in cosmic turmoil — as illustrated in a new image from NASA's Spitzer Space Telescope.
The image shows one of the most active and turbulent regions of star birth in our galaxy, a region called Cygnus X. The choppy cloud of gas and dust lies 4,500 light-years away in the constellation Cygnus the Swan. Cygnus X was named by radio astronomers, since it is one of the brightest radio regions in the Milky Way. (It should not be ...
Scripps Research scientists paint new picture of dance between protein and binding partners
2012-01-11
Jupiter, FL - Using a blend of technologies, scientists from the Florida campus of The Scripps Research Institute have painted a new picture of how biochemical information can be transmitted through the modification of a protein. Previously, scientists believed that during the pairing of proteins and their binding partners ("ligands"), proteins modified their shape while ligands remained stable. The new study shows this one-size-fits-all solution is not entirely accurate.
Instead, the situation resembles a kind of complex but carefully organized dance routine, where the ...