Spotlight

Abstract

Hartmann et al., pp. 938–942 Folate receptor expression could help predict breast cancer outcome, according to new work by Hartmann et al. The team examined 63 invasive breast cancers and found that most of the women whose tumors strongly overexpressed folate receptor experienced a recurrence of cancer. Several lines of evidence suggest that folate receptor could contribute to malignant tumor development. Folate receptor function is critical to processes required for proliferation. Overexpression has been linked to transformation, and antibodies to folate receptor have been shown to revert transformed cells to normal. Reducing the expression of folate receptor slows the proliferation of breast cancer cell lines. Because folate receptor is preferentially expressed in cancers of epithelial origin, and rarely expressed in normal cells, it presents a tantalizing possibility as a target for diagnosis and treatment. Hartmann et al. investigated this idea by comparing folate receptor expression in good- and poor-outcome breast cancers. On average, the 33 women comprising the poor-outcome group suffered recurrences after about 2 years, while the 30 women in the good-outcome group remained recurrence-free for at least 7 years. Using a tissue microarray, the researchers analyzed the expression pattern of folate receptor in samples from all 63 tumors and categorized them as strong or weak staining. Of the strong staining group, 81% saw their tumors recur, compared with 38% of the weak staining group. Although the cohort was small, the association between folate receptor staining and poor outcome was strong. These findings suggest that analysis of folate receptor expression is worth investigating further as a promising prognostic indictor and possibly a therapeutic target. Women whose breast tumors stained strongly for folate receptor generally had a poor outcome. Nelius et al., pp. 999–1008 Androgen receptor suppresses prostate tumor growth in a mouse model, finds a study by Nelius et al. The new work also demonstrates that AR exerts its antitumor activity by decreasing NFkB activity. Previous investigations have yielded contradictory information about the role of androgens in cell survival and proliferation. Under some circumstances, blocking AR hampers prostate cancer progression. Yet AR expression in prostate cancer cells that lack the receptor causes growth arrest and apoptosis. Testosterone has been shown to stimulate endothelial proliferation and vascular growth, and androgen withdrawal is a common treatment for prostate cancer. In the current paper, the authors induced AR expression in AR-null prostate cancer cells. Surprisingly, they found that AR made the cells less tumorigenic. In tumors that did form the vasculature density was low due to elevated anti-angiogenic thrombo-spondin-1 levels. AR expression also dramatically decreased NFkB activity, which diminished the expression of Bcl-2 and IL-6, causing apoptosis. Although AR is expressed in many advanced prostate cancers, most AR pathway genes are suppressed in metastatic prostate cancer, indicating that AR's targets work against cancer progression. The report indicates that continuous removal of androgen, which is a standard treatment for prostate cancer, could be improved upon by intermittent addition of androgen. Rehm et al., pp. 1132–1137 Drinkers who quit can reduce their risk of esophageal and head and neck cancers – but it takes time. A new analysis by Rehm et al. shows that 20 years of teetotaling can decrease the cancer risk to that of someone who never drank in the first place. Alcohol consumption ups the risk of cancer, especially in the esophagus and the head and neck: the heavier the drinking, the higher the risk. No one quite knows exactly how alcohol causes these cancers, and not many studies have examined what happens to cancer risk when a person stops drinking. The current work aimed to collect these studies for a pooled analysis of the existing data and establish how cancer risk adjusts over time after drinking has stopped. The researchers identified 13 unique studies on the association between alcohol drinking cessation and reduction in risk of esophageal and head and neck cancers. In their analysis, they found that esophageal cancer risk significantly increased within the first 2 years after quitting, and head and neck cancer risk remained elevated up to 10 years after drinking had ceased. These increases, the authors explain, could be due to “sick quitter” behavior, in which people stop drinking when they begin to feel some symptoms. The esophageal cancer risk began to decrease after 2 years, until after 15 years it had become virtually identical with the risk experienced by never-drinkers. Quitting drinking, the authors conclude, could play an important role in reducing cancer risk.