Combination Targeted Therapy for Liver Cancer Shows Promise in Mice ►NCI Cancer Bulletin for May 1, 2012 - National Cancer Institute

NCI Cancer Bulletin for May 1, 2012 - National Cancer Institute

Combination Targeted Therapy for Liver Cancer Shows Promise in Mice

New findings show that a combination of two drugs that act on the same target by different mechanisms is more potent than either drug alone in shrinking tumors and reversing altered gene expression in a mouse model of liver cancer. On the basis of these unexpected findings, published online April 25 in Science Translational Medicine, researchers have initiated an early-phase clinical trial of the drug combination in patients with liver cancer and other solid tumors.
The two drugs—everolimus, which is already approved for the treatment of a number of cancers, and an experimental drug being tested in clinical trials known as BEZ235—inhibit mTOR, a protein that controls cell growth, proliferation, and autophagy. The mTOR signaling pathway is overly active in many human cancers, including 40 to 50 percent of liver cancers. Everolimus and other related mTOR inhibitors, called rapamycins, are being tested in patients with liver cancer in clinical trials.
However, the rapamycins now in clinical use do not completely block the effects of mTOR signaling in cells, explained Dr. Sara Kozma of the University of Cincinnati, who led the new study. She and her colleagues originally set out to determine whether BEZ235 was more effective than the rapamycins. To their surprise, they found that the two drugs had synergistic effects when used together at low doses.
Further experiments showed that the two-drug combination increased autophagy, a process thought to suppress liver tumors, compared with a placebo or either drug alone. More studies are needed to explore how increased autophagy could contribute to tumor regression, Dr. Kozma commented.
“The fact that we could find synergy of BEZ235 with a drug that is already approved for clinical use may facilitate [BEZ235’s] introduction into the clinic,” Dr. Kozma said. Furthermore, she noted, adverse side effects would be reduced if lower doses of the two-drug combination prove effective in treating human cancers.

Also in the Journals: New Diet and Exercise Guidelines for Cancer Survivors
Cancer survivors should eat a healthy diet, get adequate physical activity, and maintain a healthy weight, according to new guidelines from the American Cancer Society (ACS). The guidelines were published April 26 in CA: A Cancer Journal for Clinicians.
The guidelines make recommendations for diet and exercise for various stages of cancer survivorship and review scientific findings on nutrition and physical activity for several common cancers. In general, a diet low in saturated fat and high in fruits, vegetables, whole grains, and protein is recommended, as is 150 minutes per week of moderate exercise or 75 minutes per week of vigorous exercise. The guidelines also include a section with frequently asked questions about alcohol, antioxidants, fat, dietary supplements, and other topics.
Further reading: “The Right Balance: Helping Cancer Survivors Achieve a Healthy Weight”