EGFR inhibitors show promise for obesity
Students’ successes in the first grade can affect more than their future report cards. In a new study, University of Missouri researchers found links among students’ weak academic performance in the first grade, self-perceptions in the sixth grade, and depression symptoms in the seventh grade. “We found that students in the first grade who struggled
Full Post: Recognizing children’s successes in all areas may prevent teenage depression
Once-promising drugs that were abandoned in the fight against breast cancer still could be effective in obese patients, new research suggests.
In laboratory tests, hormones produced by fat cells stimulate breast cancer cells to migrate and invade surrounding tissues, scientists at Emory University School of Medicine found. A class of drugs called epithelial growth factor receptor (EGFR) inhibitors could block the stimulatory effects of the hormones.
The researchers’ results are published online and are scheduled for publication in the December issue of the journal Cancer Research .
“This group of compounds was basically written off as far as breast cancer goes,” says senior author Dipali Sharma, PhD, assistant professor of oncology/hematology at Emory University School of Medicine and Emory Winship Cancer Institute.
Sharma and her colleagues have been studying the effects of leptin, a hormone produced by adipocytes (fat cells), on breast cancer cells. One of leptin’s functions is to send “had enough” signals to the hypothalamus, part of the brain that controls appetite, and it also regulates bone formation, reproductive functions and the growth of blood vessels.
Most obese people appear to produce an abundance of leptin but for them, leptin”s appetite-controlling effects are muted in ways that are poorly understood. In addition to leptin, obese people also have high levels of insulin-like growth factor-1 (IGF-1), which is produced primarily by the liver.
“The influence of obesity on breast cancer is more pronounced because most of the breast tissue is made of adipocytes,” Sharma says. “There is an increasing amount of evidence for the importance of the environment surrounding the tumor in spurring its growth.”
She and first author Neeraj Saxena, PhD, assistant professor of medicine/digestive diseases, found that together leptin and IGF-1 stimulate breast cancer cells to grow more than either does by itself. Together, they activate the EGFR molecule, the target of several anti-cancer drugs.
“Inhibiting either leptin or IGF-1 by itself would only take care of one,” Sharma says. “Instead, we thought it would be better to look downstream and see where the two pathways converge.”
Various EGFR inhibitors, such as erlotinib and cetuximab, have been approved by the FDA to treat head and neck cancer, lung cancer, colon cancer and pancreatic cancer. One, lapatinib, was approved in 2007 for women with advanced breast cancer who had already received other therapies.
However, clinical studies did not find most EGFR inhibitors effective against breast cancer for a large enough proportion of patients. Some oncologists believe it may be possible to select a fraction of patients, either through genetics or the characteristics of their tumors, who have a better chance of having the drugs work.
In the laboratory, EGFR inhibitors blocked the stimulatory effects of leptin and IGF-1 and had more of an effect on breast cancer cells’ ability to migrate and invade other tissues than on proliferation. This suggests they could blunt aggressive, metastatic tumor behavior, Sharma says.
She says her team’s finding could be especially important for “triple negative” breast cancer, a form that does not respond to tamoxifen or the drug trastuzumab. Recent studies have shown a high prevalence of triple negative breast cancer in African-American women.
To strengthen the finding, Sharma is planning more tests in animals that model cancer growth in obese individuals and careful study of leptin and IGF-1 levels in human tumor samples.
Antibodies that target epidermal growth factor receptor (EGFR) have proven themselves as potent anticancer drugs. Now, a team of investigators led by Shuming Nie, Ph.D., and Lily Yang, Ph.D., both at the Emory University School of Medicine and members of the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology, is aiming to capitalize on
Full Post: Artificial antibody delivers nanoparticles to tumors
A new study in the January 7th issue of Cell Metabolism, a Cell Press publication, helps to explain why obese people and animals fail to respond to leptin, a hormone produced by fat that signals the brain to stop eating. What’s more, they show that two FDA-approved drugs might restore leptin sensitivity, offering a novel
Full Post: Novel treatment option for obesity
In an important finding published online in Developmental Cell, researchers at Albert Einstein College of Medicine of Yeshiva University, along with collaborators at Massachusetts Institute of Technology, have identified a protein likely responsible for causing breast cancer to spread. Metastatic cancer occurs when cancer cells from the original tumor travel to distant sites via the
Full Post: Discovery of protein that may cause breast cancer to spread
Scientists at the University of Texas at Austin have identified pathways by which a reduced-calorie diet and exercise can modify a postmenopausal woman’s risk of breast cancer. The results, presented at the American Association for Cancer Research’s Seventh Annual International Conference on Frontiers in Cancer Prevention Research, suggest that both caloric restriction and exercise affect
Full Post: Reduced-calories and exercise can modify a postmenopausal woman’s risk of breast cancer
Two critical properties of cancer cells are their ability to divide without restraint and to spread away from the primary tumor to establish new tumor sites. Now, researchers from the Mayo Clinic campus in Florida have found a protein they say acts as a deadly master switch, both freeing cancer cells from a tumor while
Full Post: Scientists identify dangerous ‘two-faced’ protein crucial to breast cancer spread and growth