News from Cancer Meeting

A roundup of recent research announced this week at the annual conference of the American Association for Cancer Research (AACR).

By | April 4, 2012

image: News from Cancer Meeting Lung cancer cell with irregular bulges in the plasma membrane (purple)Flickr, Wellcome Images

Lung cancer cell with irregular bulges in the plasma membrane (purple) FLICKR, WELLCOME IMAGES

A diabetes drug that treats cancer
In the mid-2000s, epidemiologists began noticing that diabetics taking daily doses of metformin—the most widely prescribed medication for hyperglycemia and type 2 diabetes—showed decreased cancer incidence and cancer-related mortality. Originally isolated from the French lilac (Galega officinalis), metformin lowers circulating insulin through the indirect activation of AMP-activated protein kinase (AMPK)—a regulator of cellular metabolism.

At the 2012 American Association for Cancer Research (AACR) annual meeting, held in Chicago this week, several research groups presented data supporting an inhibitory role for metformin in several types of cancers. The new studies suggest metformin could be adopted for both the prevention and treatment of metformin-sensitive cancers.

In a phase II clinical trial involving 22 men with prostate cancer, for example, thrice-daily doses of 500 mg of metformin, given from the day of diagnosis until the routine prostatectomy nearly 6 weeks later, markedly reduced the size of the tumors in some of the men.

“Although these are preliminary results, metformin appeared to reduce the growth rate of prostate cancer in a proportion of men,” Anthony Joshua, an oncologist at Princess Margaret Hospital in Toronto who presented the results at the meeting on Saturday, March 31, said in a press release.

Similarly, treatment with metformin improved the survival rate of patients with both pancreatic cancer and diabetes by nearly two-fold, according to a retrospective study carried out by University of Texas researchers.

Administration of metformin to mice with premalignant oral lesions also slowed the progression of the lesions into cancers by 70 to 90 percent, a team led by National Institutes of Health (NIH) researcher J. Silvio Gutkind reported. Specifically, the team found that metformin prevented the development of the lesions into head and neck cancers by inhibiting mTORC1—a protein complex known to respond a wide array of cellular signals including growth factors, nutrients, DNA damage, and energy levels.

And in a study published yesterday (April 3) in Cancer Prevention Research, an AACR journal, researchers led by molecular biologist Geoffrey Girnun of the University of Maryland School of Medicine reported that metformin slowed tumor growth in mice with chemically induced liver cancer. They found that metformin decreased the expression of enzymes involved in lipid synthesis in the liver, an important process for tumor growth.

Inflammation and cancer

DREAMSTIME, JOHANNA GOODYEAR

Adding to the growing body of evidence linking chronic inflammation to carcinogenesis (see our April 2011 feature “An Aspirin for your Cancer?”), assistant professor at the University of North Carolina in Charlotte Lopamudra Das Roy presented on April 1 the results of a preclinical study showing that mice suffering from arthritis—a chronic inflammation of the joints—are more likely to develop metastatic breast cancer.

Aiding the metastasis of breast cancer tumor cells to other organs are innate immune cells known as mast cells, Das Roy said. Mast cells are normally involved in wound healing and pathogen defense but can be activated when a tumor secreted cytokine called stem cell factor (SCF) binds to the mast cells’ c-Kit receptor. Once activated, mast cells produce proinflammatory factors associated both with arthritis and metastasis.

Blocking the c-Kit receptor in the mast cells of arthritic mice, in conjunction with treating arthritis inflammation, reduced the spread of breast cancer to the bones and lungs, Das Roy found.

“We already have data that show that women with breast cancer and arthritis have lower survival as compared with women with breast cancer and no arthritis,” Das Roy said in a press release. “This research indicates that we may be able to design a therapy to block SCF/c-Kit signaling, which could help reduce metastases to the bone and lungs.”

In another study presented on April 3, researchers found that reducing weight and inflammation through exercise and caffeine consumption reduced the appearance of sun-induced skin cancer by 62 percent in a skin cancer-prone mouse model. Routine exercise and caffeine intake reduced inflammation by more than 90 percent in those mice, suggesting a key role for inflammation in the progression of ultraviolet light-induced skin cancer.

“I believe we may extrapolate these findings to humans and anticipate that we would benefit from these combination treatments as well,” Yao-Ping Lu, director of skin cancer prevention at the Rutgers Ernest Mario School of Pharmacy who led the study, said in a press release.

The hazards of smoking

DREAMSTIME, RAJESH PATTABIRAMAN

Tobacco may increase the levels of toxic estrogen metabolites in the lungs, Fox Chase Cancer Center researchers stated at the AACR meeting on April 3. Estrogen has been previously linked to several cancer types in women and was added to the NIH’s known list of carcinogens back in 2002. Several metabolites of the hormone are carcinogenic and are known to promote cell proliferation and damage surrounding tissue, among other things.

One such toxic metabolite is 4 hydroxy- estrogens (4-OHEs), which researchers found was increased in the lungs of mice exposed to tobacco smoke over the course of several weeks. "We believe that these metabolites of estrogen can damage cells and contribute to lung cancer," Margie L Clapper, a Fox Chase cancer biologist and one of the co-authors of the study, said in a press release.

Meanwhile, another group of researchers identified a chemical in smokeless tobacco that can act as a strong carcinogen. (S)-N’-nitrosonornicotine, or (S)-NNN for short, induced tumors in the tongue, oral mucosa, soft palate, and pharynx of mice.

“This finding provides mechanistic underpinning for the epidemiologic observations that smokeless tobacco products cause oral cancer,” Silvia Balbo, a research associate at the University of Minnesota who presented the study, said in a press release.

Chemotherapy goes nano
Researchers at Cambridge-based pharmaceutical company BIND Biosciences presented data from an ongoing phase I clinical trial of a nano drug for treating advanced or metastatic solid tumor cancers. Known as BIND-014, the drug belongs to a class of targeted nanotherapeutics currently being developed by the company.

BIND-014 is essentially a miniaturized version of the well-established chemotherapeutic drug docetaxel—commonly used to treat advanced or metastatic breast and non small-cell lung cancers. It contains docetaxel in a nanoparticle coated with molecules that selectively target tumor tissue.

In a trial of 17 patients with advanced or metastatic cancer, including cervical, pancreatic, colorectal, bile duct, tonsillar, and anal cancers, researchers found that BIND-014 displayed antitumor activity even in cancers that were not responsive to regular docetaxel treatment.

Additionally, in vivo experiments of BIND-014 in a prostate-cancer mouse model, reported today (April 4) on Science Translational Medicine, showed that BIND-014 is highly selective for cancerous tissue and has minimal accumulation in the liver.

“The emerging BIND-014 clinical data are showing exciting signals of activity, validating the potential for the revolutionary impact of nanomedicines for the treatment of cancer,” Philip Kantoff, Chief Clinical Research Officer at the Dana-Farber Cancer Institute, said in a press release.

Correction (April 9, 2012): The original feature image of this story was incorrectly labeled as cancer neck cells when in fact it was an image of viral particles. The image has been replaced. The Scientist regrets the error.

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Avatar of: RonHorgan

RonHorgan

Posts: 8

April 6, 2012

Another example of the role of inflammation in carcinogenesis may be the effect of asterxanthin in removing solar keratosis. As this condition ,"age spots" is a precancerous change the removal may also apply to other less obvious sites of precancerous damage.
Asterxanthin is a powerful antioxidant and it seems to me that antioxidants are often also antiinflammatories.
I took 4 mg daily and almost all of the prominent keratoses on my forearms faded away in 2-3 months.
Wound healing may also be delayed by episodes of inflammation and scarring.
I had surgery for an badly torn rotator cuff. the usual course of recovery involves physiotherapy with ice packs to reduce the swelling as the joint is mobilized.
I healed in about a third of the usual time without the swelling and pain, possibly as a result of taking krill oil containing asterxanthin along with fish oil vitamins E and C etc.
Anecdotes sure but it worked for me.

Avatar of:

Posts: 0

April 6, 2012

Another example of the role of inflammation in carcinogenesis may be the effect of asterxanthin in removing solar keratosis. As this condition ,"age spots" is a precancerous change the removal may also apply to other less obvious sites of precancerous damage.
Asterxanthin is a powerful antioxidant and it seems to me that antioxidants are often also antiinflammatories.
I took 4 mg daily and almost all of the prominent keratoses on my forearms faded away in 2-3 months.
Wound healing may also be delayed by episodes of inflammation and scarring.
I had surgery for an badly torn rotator cuff. the usual course of recovery involves physiotherapy with ice packs to reduce the swelling as the joint is mobilized.
I healed in about a third of the usual time without the swelling and pain, possibly as a result of taking krill oil containing asterxanthin along with fish oil vitamins E and C etc.
Anecdotes sure but it worked for me.

Avatar of:

Posts: 0

April 12, 2012

 The highly sophisticated instruments and techniques could lead to a new understanding of cancer development.some drugs which was early used as antibiotic is now used to treat leukemia cancer .Recently a team of scientist discovered that its stops the angiogenesis of tumor cells  

Avatar of: Shabu Shaik

Shabu Shaik

Posts: 1457

April 12, 2012

 The highly sophisticated instruments and techniques could lead to a new understanding of cancer development.some drugs which was early used as antibiotic is now used to treat leukemia cancer .Recently a team of scientist discovered that its stops the angiogenesis of tumor cells  

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