Nature Medicine

The receptor for testosterone mediates resistance to chemotherapy for prostate cancer, Charles Sawyers and colleagues report in the January issue of Nature Medicine.

Most prostate cancer patients receive drugs to block production of androgens (a group of steroids that includes testosterone), which promote cancer cell growth. Although initially effective, the therapy eventually fails when the cancers progress to a lethal drug-resistant state. Sawyers and colleagues found that expression of the androgen receptor is two- to fivefold higher in those cancers, compared with the more hormone-sensitive form. This increase in androgen receptor makes drug-resistant cancer cells sensitive to even low levels of androgen, defeating the purpose of the antiandrogen therapy.

The authors also shed light on why antiandrogens in resistant cancers promote androgen receptor function rather than inhibiting it. Their findings may help in the development of new antiandrogens that are not susceptible to drug resistance.

Nature Medicine

In the January issue of Nature Medicine, Ali Brivanlou and colleagues report an important first step toward producing human embryonic stem cells (HESCs)—which would be suitable for medical use—without using mouse feeder cells.

HESCs hold great promise for regenerative medicine. But an obstacle to their use has been the need to maintain them in culture using mouse feeder cells, or conditioned medium from those feeder cells. Brivanlou and colleagues discovered a method of growing HESCs without the use of feeder cells.

By turning on an important signaling pathway, a small-molecule inhibitor of the protein glycogen synthase kinase-3 can maintain HESCs as undifferentiated, dividing cells. Upon removal of the inhibitor, the HESCs can differentiate into multiple cell types, both in cell culture and when implanted into a mouse. The results provide new insight into the fundamental signaling mechanisms that underlie the unique characteristics of embryonic stem cells.