Israeli discovers cancer's molecular trigger

Also in this week's Health Scan: A new type of diet pill.

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November 3, 2007 19:27
3 minute read.
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Although the exact cause of cancer remains a mystery, scientists have learned a great deal about it in the past few decades by looking at the molecular level. Prof. Uri Nir, vice dean of Bar-Ilan University's life sciences faculty, has discovered a "smoking gun" - an enzyme that, in several tissue types, plays a pivotal role in the onset and progression of cancer. "In normal tissues, there's a balance between signals that cause cells to replicate and other signals that arrest growth and program cell death," Nir explains. "In cancer, this balance is tipped so that cells start to replicate uncontrollably. It turns out that an important regulator of this 'tipping point' is an enzyme called Fer. In our lab, we've identified a Fer-based process that occurs only in abnormal cells," he says. "This process is required for the proliferation of abnormal cells in colon, prostate and breast cancers. The fact that the same mechanism appears in all these cancers indicates that we may have found an important molecular junction where normal tissues turn cancerous." Nir's conclusions about what turns cancer "on" were reached using genetic techniques that allowed him to deactivate the Fer enzyme. "We've shown that without the enzyme, the proliferation of prostate carcinoma cells in tissue culture is halted. We've had similarly encouraging results using breast and colon cancer cells," reports Nir. Indeed, his group recently discovered that down-regulation of Fer inhibits the progress of prostrate tumors in animals. Nir's work is important because it provides a clear target to develop new anti-cancer drugs. "We are looking for a compound that can bind to the Fer enzyme and prevent it from interacting with other molecules," he says, adding that he is working on a robotic technique to screen for potential Fer inhibitors, making the whole process faster than conventional drug discovery. "If we are successful, it may be possible to use the molecule we find to 'short-circuit' the process that leads to cancer." Nir, in collaboration with two other Bar-Ilan researchers, chemistry Prof. Geraldo Byk and biophysicist Dr. Yoav Paas, is working on techniques in which anti-cancer drugs would be attached to a cancer-seeking nanovehicle. By putting drugs exactly where they are needed, Nir explains, it will be possible to achieve better results with lower doses. "The uniqueness of our program is in the way it combines academic studies with real-life, practical work in a wide range of biotech companies," says Nir, who heads the Bar-Ilan's graduate program in biotechnology. "Students perform research under an advisor from the life sciences faculty and a supervisor from industry. Biotechnology is by its very nature multidisciplinary, and the program's curriculum - which includes training in intellectual property law, ethics and business management along with straight science - prepares graduates to be leaders in this growing area of the Israeli economy." A FAR BETTER DIET PILL? More than 60 percent of American women are overweight, with nearly a third obese and thus at greater risk of cancer, heart disease and diabetes, and Israeli women at not far behind. Now Dr. Nir Barak of Tel Aviv University's Sackler School of Medicine has developed Histalean, which could be an effective weight-loss drug. Working with the drug company Obecure, Barak developed it based on betahistine, a drug marketed for the treatment of vertigo that has been on the market for over 30 years. Betahistine is believed to block receptors in the brain - the H1 and H3 receptors - connected to one's sense of fullness and desire to eat fatty food. It has an excellent safety profile, having been used by more than 100 million patients suffering from vertigo and dizziness in Canada and Europe, Barak says. The repurposed pill, Histalean, has been found to quell the desire to consume fatty foods, and the effects are most pronounced in women. A recent Phase II clinical trial in the US that included 281 patients aged 18 to 65 suggests that women under 50 who took Histalean for 12 weeks lost seven times more weight than those taking a placebo, and none complained of serious side effects. The recent results were based on a double-blind, placebo-controlled study on people with a body mass index ranging from 30 to 40 (a BMI of 30 and above indicates obesity.) The study was conducted at 19 sites across the US. The subgroup of high-dose Histalean-treated women lost an average of 2.91% of their weight versus the placebo group, which lost only 0.4 %. The women who took the pill reported that the trial wasn't difficult, and that they weren't thinking about food all the time.

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