Also in the June 10 JNCI

Novel Targeted Therapy Reduces Chemoresistance in Mouse Model of Melanoma A novel small molecule inhibitor reduced both endogenous and drug-induced resistance to chemotherapy in a mouse model of melanoma.

The NF-κB pathway is often active in human cancers and promotes resistance to cytotoxic chemotherapy drugs. Some cytostatic drugs, such as doxorubicin, induce NF-κB pathway activity.

To determine if a new inhibitor of the pathway, called KINK-1, could overcome this resistance, Michael Schön, M.D., of the University Medical Center Göttingen in Germany and colleagues injected mice with melanoma cells and then treated them with doxorubicin and KINK-1.

They found that mice treated with a combination of the two drugs developed smaller lung metastases than mice treated with either agent alone.

"Based on our observation that the compound suppressed constitutive NF-κB activation and NF-κB activation induced by cytostatics or inflammatory agents, KINK-1 appears to be a universal inhibitor of NF-κB activation in melanoma cells, regardless of the mode of activation," the authors write.

In an accompanying editorial, John Kirkwood, M.D., of the University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute and colleagues review the biology of NF-κB and its impact on melanoma cells. Other inhibitors of the pathway have been tried in melanoma and did not prove successful. The KINK-1 inhibitor blocks the pathway in a different manner and may have a bigger impact on the disease, though that must be tested in a clinical trail. "These new agents may be most beneficially combined with chemotherapeutic agents to which melanoma has been refractory in the past," the editorialists conclude.

Contact:

• Article: Michael Schön, michael.schoen@med.uni-goettingen.de, +49-551-39-6401

• Editorial: John Kirkwood, KirkwoodJM@upmc.edu, (412) 623-7708

Low Melatonin Associated with Increased Risk of Breast Cancer in Postmenopausal Women

Low melatonin levels are associated with an increased risk of breast cancer in postmenopausal women, according to a prospective case-control study.

Melatonin is primarily secreted during the dark hours of a light-dark cycle and has been shown to be low in some night workers. Researchers have found that low melatonin levels in premenopausal women are associated with an increased risk of breast cancer.

To find out if a similar association occurs in postmenopausal women, Eva Schernhammer, M.D., Dr.P.H., of the Brigham and Women's Hospital and Harvard Medical School in Boston and colleagues compared melatonin levels in 178 postmenopausal women and 710 matched controls. All of the women were enrolled in the prospective Hormones and Diet in the Etiology of Breast Cancer Risk study.

The researchers found that women with the lowest levels of melatonin had a statistically significantly higher incidence of breast cancer than those with the highest levels.

The researchers conclude that low melatonin levels are associated with an increased risk of breast cancer. Further studies need to confirm these data and should investigate the mechanisms that underlie the association.

Contact: Lori Shanks, ljshanks@partners.org, (617) 534-1604

Source: Journal of the National Cancer Institute