March 2012 Archives

Abnormal activation or production of four proteins involved in translation, the final step of creating other proteins, are associated with reduced survival among patients with hormone receptor-positive breast cancer.

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Findings presented at the AACR Annual Meeting 2012 in Chicago, if validated in additional research, could lead to new prognostic indicators, new targets for drugs, and better selection of patients for existing therapies.

All of the aberrantly activated translational proteins are regulated by the PI3K/mTOR molecular signaling pathway, which has been implicated in development and progression of various cancers and in resistance to standard endocrine therapy in estrogen-receptor positive breast cancer.

"These data underline the importance of the PI3K/mTOR pathway in hormone receptor-positive breast cancer," says Funda Meric-Bernstam, M.D., professor in MD Anderson's Department of Surgical Oncology and medical director of the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy.

Teaming Up Two Drugs Helps Ewing's Sarcoma Patients

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Naing.jpg A combination of two targeted therapies reduces tumors in treatment-resistant Ewing's sarcoma, a bone cancer that mainly strikes children, adolescents and young adults.

Results of the phase I  clinical trial of the paired drugs were announced today at a news briefing at the AACR Annual Meeting 2012 by Aung Naing, M.D., assistant professor in MD Anderson's Department of Investigational Cancer Therapeutics. He presents the study Monday during the meeting's session on late-breaking clinical trials.

"These patients had been heavily, heavily pre-treated and are quite resistant to most other treatments," Naing said. "So we are encouraged that 5 of 17 patients with Ewing's sarcoma, about 29 percent, responded to the treatment, with two achieving complete responses."

One complete response lasted 27 months. Two of three patients with desmoplastic small-round-cell tumors also responded.                                                    

Researchers used a combination of cixutumumab, a human IgG1 monoclonal antibody that targets insulin growth factor receptor 1 (IGF-1R), and temsirolimus, an agent that inhibits mTOR, the mammalian target of rapamycin.

renataPasqualini.jpgAn innovative approach to targeting the blood vessels that support neuroendocrine tumors of the pancreas has earned the support of a major grant in the field.

The American Association for Cancer Research will award Renata Pasqualini, Ph.D., MD Anderson's David H. Koch Center for Applied Research of Genitourinary Cancers with the 2012 Caring for Carcinoid Foundation-AACR Grant for Carcinoid Tumor and Pancreatic Neuroendocrine Tumor Research.

The grant will be given during a reception Tuesday, April 3 at the AACR Annual Meeting 2012 in Chicago.

Created in partnership between AACR and the Caring for Carcinoid Foundation, the two-year grant of $250,000 ($125,000 per year) supports investigators as they develop and study new ideas and innovative approaches that have direct application and relevance to carcinoid tumors or pancreatic neuroendocrine tumors.

AACR Honors Mendelsohn for 'Extraordinary Achievements'

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The American Association for Cancer Research will present its sixth annual AACR Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research to John Mendelsohn, M.D., at the association's annual meeting opening session this Sunday in Chicago.

119809_Mendelsohn_J.jpgMendelsohn is co-director of MD Anderson's Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (IPCT) and was president of MD Anderson from 1996 to 2011.

The award, announced today, recognizes a person who has had a major impact by conducting or supporting cancer research. 

"Dr. Mendelsohn was a pioneer in the area of targeted cancer therapies, specifically working with EGFR tyrosine kinase inhibition," said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. "The AACR commends him for his groundbreaking research on targeted therapy, which opened the door to a new way of thinking about cancer and its treatment. In addition, Dr. Mendelsohn is both a nationally and internationally recognized leader in cancer policy."

 

The award is named for Foti, who has been chief executive officer of AACR, the world's oldest and largest cancer professional organization, since 1982.

Low Dose Aspirin And Cancer Risk

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By: Raymond DuBois, M.D., Ph.D.

Aspirin and cancer riskWe have known for the past two decades that aspirin and non-steroidal anti-inflammatory drug (NSAID) use reduces the risk of colorectal and other cancers. Today the Lancet published new reports indicating that low dose daily aspirin reduces the risk of distant metastasis of several cancers (Lancet Early Online Publication.)

The data came from 51 trials that included over 77,000 patients.

This protective effect appears to occur within 3-5 years of beginning aspirin use. It was previously thought that this protective effect would take up to 10 years to have an impact. These trials were originally designed to compare aspirin with no treatment for the prevention of heart disease.

In carefully looking at the data it became apparent that regular aspirin use reduced the risk of colorectal cancer as well as esophageal, gastric, biliary and breast cancer. People using 75-300 mg per day were found to have a significant reduction in the total number of cancer cases. Aspirin also reduced the risk of cancer death by 15% within 5 years and people using aspirin for longer duration had a 37% reduction in risk.

Researchers have caught two molecular signaling networks engaged in "crosstalk" that undermines attempts to successfully target cancer-promoting abnormalities in esophageal cancer.

 

Writing in the March 20 edition of the journal Cancer Cell, the team shows how the mTOR and Hedgehog pathways converge on the activity of a single protein, called Gli1, and how this conversation can be interrupted with a combination of drugs already approved by the U.S. Food and Drug Administration for certain types of cancer.

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"Crosstalk between these two pathways is a challenge, but our experiments showed a combination of the mTOR inhibitor RAD-001 (Afinitor®) and the Hedgehog inhibitor GDC-0449 (Erivedge®) steeply reduced the tumor burden in a mouse model of esophageal adenocarcinoma," says senior author Mien-Chie Hung, Ph.D., MD Anderson vice president for basic research and chair of the Department of Molecular and Cellular Oncology.

 

Esophageal cancer is one of the most aggressive forms of cancer, with fewer than 20 percent of patients surviving for five years, the study notes. And it has become more frequent in the United States by 5 to 10 percent annually since the 1980s. Inflammation and obesity are thought to be driving factors in this increased incidence, Hung said.

 

The researchers used experiments with cell lines, mouse models and human tumor samples to demonstrate how Hedgehog and mTOR activate Gli1 in different ways to promote esophageal cancer development and progression.

 

The two drugs together reduced the tumor burden of mice with esophageal cancer by 90 percent, suggesting that the combination merits testing in human clinical trials, Hung said.

 

The Hedgehog inhibitor GDC-0449 was approved by the FDA in January for basal cell carcinoma. Basal cell carcinoma is driven by mutations in the Hedgehog pathway, Hung says, but resistance to these inhibitors has emerged in clinical trials to treat other cancers, such as ovarian and pancreas.  "We now believe the mTOR pathway is one source of this resistance." 

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Additional information

 

MD Anderson news release

Cancer Cell paper

 

 

 

smokingdeclineimage.jpgBy Katrina Burton, MD Anderson Staff Writer

Tobacco use has long been known to cause lung cancer and increased morbidity in smokers. A study sponsored by the National Cancer Institute (NCI) recently revealed the positive impact of U.S.-initiated tobacco control policies and programs with the prevention of 795,000 lung cancer deaths from 1975 through 2000.

Researchers at MD Anderson and Rice University collaborated as one of six lung cancer modeling groups for the NCI-sponsored Cancer Intervention and Surveillance Modeling Network Consortium. They applied a comparative modeling approach in which detailed smoking histories of 30- to 84-year-olds born from 1890 to 1970 were related to lung cancer mortality in mathematical models.

Using these models, researchers analyzed the impact of changes in smoking patterns resulting from tobacco control activities initiated after the U.S. Surgeon General's Report on Smoking and Health was released in 1964.
By Katrina Burton, MD Anderson Staff Writer

At an early age, children are naturally physically active, full of energy and often find joy in running and jumping in an unstructured environment. However, as children transition to adolescence, physical activity levels tend to decline, particularly among girls. This is also a time when excess weight gain often occurs.

Physical inactivity and obesity are important risk factors for a variety of cancers, and behaviors developed during adolescence can persist into adulthood. Identifying factors that contribute to physical activity during this critical stage of development may help future efforts to promote continued activity among adolescents. Mexican-American adolescents exhibit an increased prevalence of obesity compared to other adolescent populations.

So what are the factors that influence physical activity and sedentary behaviors in Mexican-American adolescents? Researchers at MD Anderson Cancer Center's Division of Cancer Prevention and Population Sciences are studying social, cultural and environmental factors that are believed to be important in answering this question.


fuelberg2 web2.JPGMyelofibrosis, a lethal bone marrow malignancy, comes with especially debilitating symptoms that sap a patient's quality of life. 

Jeanie Fuelberg, of Dripping Springs, Texas, had them all.

"I was having trouble breathing. My liver was enlarged. I couldn't eat because my spleen was so huge.  I lost lots and lots of weight.  There was an intense itching - if you can imagine an itching sensation inside your body.  I had night sweats, abdominal pain and was extremely tired all of the time," she says.

"I had been told by my hematologist that I did not have much time to live."

When she enrolled in a phase III clinical trial at MD Anderson in October 2009, she was told the study drug was likely to ease her symptoms and improve her quality of life if she received it in the randomized, blinded placebo study.  It would not cure the illness.

Fuelberg began to feel better within two weeks. "My health has improved tremendously and most symptoms have stopped.  And there've been no bad side effects.  They told me that it would not prolong my life, but I think it has because I'm doing so much better."

Her impression has been confirmed by data from the study, which shows that the drug ruxolitinib, known commercially as Jakafi ®, improves survival of myelofibrosis patients.  Clinical trial results for the drug made by Incyte Corporation were published recently in The New England Journal of Medicine.

Principal investigator of the COMFORT1 study, which enrolled 309 patients in 89 centers across the United States, Canada and Australia, was Srdan Verstovsek, M.D., Ph.D., associate professor in MD Anderson's Department of Leukemia.

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