BLOCKING ENZYME COULD HELP IN RARE BLOOD CANCER

An enzyme that fights some kinds of cancers may foster the growth of a rare type of leukemia that affects babies, U.S. researchers said on Wednesday in a finding that may lead to new drugs for the hard-to-treat cancer.

They said drugs that blocked the enzyme glycogen synthase kinase, or GSK3, helped mice with mixed-lineage leukemia, or MLL, live far longer than untreated mice.

The finding is a surprise because prior studies have found GSK3 helped suppress unchecked cell growth in other cancers.

"GSK3 has never been implicated in promoting cancer," said Dr. Michael Cleary of Stanford University in California, whose research appears in the journal Nature.

Cleary's team found that blocking GSK3 fights leukemias caused by mutations in the MLL gene, which accounts for 5 percent to 10 percent of child and adult leukemias and more than three-quarters of leukemias diagnosed in infants.

Cleary said only a few hundred people in the United States get MLL each year, but when babies get leukemia, they tend to get this form, although it is not clear why.

While most leukemias get their start in either lymph nodes or bone marrow, MLL cancer cells can originate from both.

"These patients don't typically respond well to chemotherapy. There is a real need for better treatments," Cleary said in a telephone interview.

His team first got a hint that blocking GSK3 might fight MLL through routine screening tests in the lab.

The researchers gave the mice with MLL lithium, a drug used to treat bipolar disease in humans.

"It is not the best GSK3 inhibitor, but it is one that could be administered long-term in mice," Cleary said.

Mice treated with the lithium lived significantly longer than the untreated mice. Cleary's team also used a different GSK3 inhibitor in MLL cells and found it stopped them from growing.

"I think where we need to go in the future is to come up with better inhibitors that can be administered long-term," Cleary said.

That may come through research of the drug in other diseases. Cleary said drug companies are developing GSK3 inhibitors as treatments for diabetes and Alzheimer's disease.

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BREATHING DISORDER PUTS BLACKS AT HIGH CANCER RISK.

"Blacks with a history of the chronic breathing disorder COPD have a far greater risk of developing lung cancer than whites who have the lung disease, U.S. researchers said on Thursday.

They said the high risk for blacks with chronic obstructive pulmonary disease highlights the need for better risk assessment tools that take race and ethnicity into account.

'The one-size-fits-all risk prediction clearly does not work,' Carol Etzel of the University of Texas M.D. Anderson Cancer Center, whose report appears in the journal Cancer Prevention Research, said in a statement.

Etzel's team developed the risk assessment tool for African Americans to help doctors better predict a patient's specific risk for lung cancer.

They analyzed data from 491 African Americans with lung cancer and 497 African Americans without lung cancer to look for risk factors. They compared these with existing risk models for whites.

The new model found black men with a prior history of COPD had a more than sixfold increased risk of lung cancer, on par with someone who is actively smoking."

RESEARCHERS IDENTIFY PROMISING CANCER DRUG TARGET IN PROSTATE TUMORS

Scientists at Dana-Farber Cancer Institute report they have blocked the development of prostate tumors in cancer-prone mice by knocking out a molecular unit they describe as a "powerhouse" that drives runaway cell growth.

In a letter appearing in an advanced online publication by the journal Nature, the researchers said the growth-stimulating molecule called p110beta — part of a cellular signaling network disrupted in several common cancers — is a promising target for novel cancer therapies designed to shut it down. The report's lead authors are Shidong Jia, Zhenning Liu, Sen Zhang, and Pixu Liu.

The p110beta molecule and a counterpart, p110alpha, are "isoforms" — slightly different forms — of an enzyme called PI(3)K that is an intense focus of cancer research and drug development. PI(3)K is the linchpin of a cell-signal pathway that responds to growth factor signals from outside the cell.

When activated by growth factor receptors, PI(3)K turns on a cascade of genes and proteins that drives cells to divide and grow. The molecular accelerator is normally kept under control by a tumor-suppressor protein, PTEN, which acts like a brake to curb excess cell growth that could lead to cancer.

Mutations that inactivate PTEN — in effect releasing the brake on growth signals — are found in a significant proportion of prostate cancer, breast cancer, and brain tumors. The senior authors of the new report, Jean Zhao and Thomas Roberts, previously showed that blocking p110alpha protein inhibits cancerous growth induced by various cancer-causing proteins, such as Her2 and EGFR. With that knowledge in hand, the researchers, in collaboration with pharmaceutical companies, are developing p110alpha blockers.

P110beta, by contrast, was thought to be a relatively insignificant player in tumors. However, "the surprise in this paper is that p110beta has been found to be a bigger player than p110alpha in tumors that result from PTEN loss," noted Zhao. "Now the drug companies, which have been focusing on p110alpha, will have to think about making p110beta inhibitors as well."

Both forms of the p110 molecule have dual tasks: they are involved in responding to insulin signals — a metabolic function — as well as relaying growth signals from outside the cell. But the importance of 110beta had been vastly underestimated, the researchers said, for reasons they don't entirely understand.

"We knew that when cells are stimulated with growth factor signals, the activity of p110alpha, but not p110beta, rises rapidly and sharply in triggering excess cell growth," Zhao said. "We speculate that p110beta may be providing a low-level but steady growth stimulus, and when PTEN is lost, it becomes an important source of cell proliferation signals."

The new findings stem from experiments in which the scientists disabled the p110beta protein in mice as a way of exploring its normal functions. In one of the experiments, the researchers "knocked out" p110beta in mice that also lacked the PTEN tumor suppressor protein and were therefore highly prone to prostate cancer. Mice that lacked PTEN but had functioning p110beta proteins all developed early prostate cancers by 12 weeks of age. In contrast, the "knockout" mice with no p110beta function remained free of prostate cancer even though the PTEN "brake" had been disabled.

The scientists concluded, as a result, that p110beta becomes a "powerhouse" to drive cancerous cell growth when PTEN function is missing.

In light of the new findings, there is likely to be great interest in finding drugs or other tools to block the p110beta protein in cancers where mutations in PTEN have unleashed the overactive growth signals, said Zhao.

The task is made somewhat easier, explained Roberts, by the fact that "we know what the inhibitor should look like because of our work on p110alpha inhibitors."

Roberts said that drugs designed to block the p110alpha form are on their way to clinical testing, but he could not predict when p110beta inhibitors might become available for clinical testing.

BREATHING DISORDER PUTS BLACKS AT HIGH CANCER RISK.

Blacks with a history of the chronic breathing disorder COPD have a far greater risk of developing lung cancer than whites who have the lung disease, U.S. researchers said on Thursday.

They said the high risk for blacks with chronic obstructive pulmonary disease highlights the need for better risk assessment tools that take race and ethnicity into account.

"The one-size-fits-all risk prediction clearly does not work," Carol Etzel of the University of Texas M.D. Anderson Cancer Center, whose report appears in the journal Cancer Prevention Research, said in a statement.

Etzel's team developed the risk assessment tool for African Americans to help doctors better predict a patient's specific risk for lung cancer.

They analyzed data from 491 African Americans with lung cancer and 497 African Americans without lung cancer to look for risk factors. They compared these with existing risk models for whites.

The new model found black men with a prior history of COPD had a more than sixfold increased risk of lung cancer, on par with someone who is actively smoking.

The risk is about twice as high as that typically seen in whites with a history of COPD, which includes emphysema, chronic bronchitis and some types of serious chronic asthma.

Smoking is by far the leading cause of COPD, but environmental factors including pollution play a role.

Blacks and white smokers both have six times higher risk of lung cancer than non-smokers. And blacks with hay fever are 44 percent less likely to get lung cancer than other blacks, a finding that has also been seen in whites.

Etzel's team is now working on a risk assessment model for Hispanics.

"What we hope is that a doctor can use these models to encourage their patients to take steps to prevent lung cancer. Even if they are never smokers, they can be at risk," Etzel said.

Lung cancer is the leading cancer killer worldwide, with almost 1.2 million deaths per year -- 162,000 deaths a year in the United States alone.

The National Cancer Institute estimates that 15,000 people who have never smoked die every year from lung cancer in the United States.

IMAGING A PROMISING CANCER DETECTOR

A radioactive tracer that "lights up" cancer hiding inside dense breasts showed promise in its first big test against mammograms, revealing more tumors and giving fewer false alarms, doctors have reported.

The experimental method — molecular breast imaging, or MBI — would not replace mammograms for women at average risk of the disease.

But it might become an additional tool for higher risk women with a lot of dense tissue that makes tumors hard to spot on mammograms, and it could be done at less cost than an MRI, or magnetic resonance imaging. About one-fourth of women 40 and older have dense breasts.

"MBI is a promising technology" that is already in advanced testing, said Carrie Hruska, a biomedical engineer at the Mayo Clinic in Rochester, Minn., which has been working on it for six years.

She gave results in a telephone news briefing Wednesday and will present them later this week at an American Society of Clinical Oncology conference in Washington, D.C.

Mammograms — a type of X-ray — are the chief way now to check for breast cancer. MBI uses radiation, too, but in a different way. Women are given an intravenous dose of a short-acting tracer that is absorbed more by abnormal cells than healthy ones. Special cameras collect the "glow" these cells give off, and doctors look at the picture to spot tumors.

Researchers tried both methods, on 940 women who had dense breasts and a high risk of cancer because of family history, bad genes or other reasons.

Thirteen tumors were found in 12 women — eight by MBI alone, one by mammography alone, two by both methods and two by neither. (The two missed cancers were found on subsequent annual mammograms, physical exams or other imaging tests.)

Looked at another way, MBI found 10 out of 13 tumors, missing three; mammograms detected three out of 13 tumors and missed 10. Using both methods, 11 out of 13 tumors would have been detected.

"These images are quite striking. You can see how the cancers would be hidden on the mammograms," Hruska said.

Mammograms gave false alarms — led doctors to conclude that cancer was present when it was not — in about 9 percent of patients, compared to only 7 percent for MBI. The MBI tests led to more biopsies than mammograms did, but they more often revealed cancer.

The Susan G. Komen for the Cure foundation and Bristol-Myers Squibb, which makes the imaging agent used in the study, paid for the work.

The next test will be to see how MBI stacks up against MRI. The federal government is paying for a new study Mayo is leading that compares the two in 120 high-risk women with dense breasts.

MRI is often used now for women with dense breasts, but it gives many false alarms that lead to unnecessary biopsies. Doctors hope MBI will prove more accurate and cost less — under $500 versus more than $1,000 for an MRI.

"We all know that mammography is, in and of itself, an imperfect tool, and we clearly need to do better in the future," said Dr. Eric Winer of the Dana-Farber Cancer Center in Boston, a spokesman for the oncology group. "It is fair to say that MRI will not solve all problems either."

One drawback of MBI: It uses about 8 to 10 times the radiation of mammograms, a dose that engineers like Hruska are trying to lower with newer technology. Other medical centers also are testing MBI.

"We're just beginning to see what this technology can do," she said.