Hair on a man’s head offers clues about versatility of a molecule central to Advanced Prostate Cancer.

Once again, those of us fighting advanced and recurrent prostate cancer are confronted with contradictory and confusing information. The usual first line treatment for advanced prostate cancer is hormone therapy (ADT). We all know that ADT is short lived in effectiveness as our cancer will become androgen independent and continue to progress, despite the therapy. According to the literature, ADT will be generally be effective for only two years before becoming androgen independent. Of course, there are individual differences, some men never gain any control of their cancer with ADT while others are able to experience successful control for many years.

It was recently discovered that sometimes the ADT drugs will actually spur some of the prostate cancers to grow, not what we really want! This shocking information was published online this week in The Findings of the Proceedings of the National Academy of Sciences. These information might help explain why ADT eventually becomes hormone independent.

Chawnshang Chang, Ph.D., director of the George Whipple Laboratory for Cancer Research at the University of Rochester Medical Center, explained the process by showing that the androgen receptor, through which male hormones like testosterone attach to the prostate cancer cells, is very versatile. Sometimes, the molecule spurs prostate cell growth, while other times the molecule halts the prostate cancer cell growth. He explained that this phenomenon was similar to the situation when the same molecule has different effects in hair growth depending upon the location of the molecule on a man’s head.

This frightening new findings raises the concern that under some conditions, some treatments (ADT) designed to treat prostate cancer could instead be removing one of the body’s natural brakes on the spread of the disease in the body and promote cancer growth. The researchers stressed that these results are based only on laboratory studies and on findings in mice. It is yet too soon to know if these findings apply directly to prostate cancer in men.

Chang’s team found that blocking the androgen receptor does prevent some cells in the prostate from continueing to grow. The big surprise was they also discovered that blocking the receptor in some situations actually encourages other prostate cancer cells to grow.

Chang said “The androgen receptor acts differently in different cells in prostate tissue. It’s always been assumed that blocking the androgen receptor will stop all prostate cells from growing, but we have found that that’s not the case. Since current treatment acts non-specifically on all the cells having androgen receptors in the prostate, blocking the androgen receptor will give mixed results.” Or, encourage the cancer to become androgen independent.

The unexpected discovery was that the androgen receptors in prostate cells known as stromal cells actually stimulates growth of cells, including cancer cells, in the prostate. In the converse they also found that the receptor actually acts as a tumor suppressor in epithelial cells known as basal cells in the prostate.

They then knocked out the androgen receptor in specific sets of prostate cells and studied the results. As expected, when the molecule is turned off in stromal cells, growth of cancer cells in the prostate slows. But when the molecule is turned off in the epithelial cells, it removes one of the body’s natural inhibitors that prevents prostate cancer cells from spreading, making cells more likely to invade other tissues.

The conclusion is that the androgen receptor both can drive prostate cancer and it also appears that the receptor inhibits the spread of cancer cells depending on the type of cell to which they are attached. Androgen receptors seems to have a dual and sometimes conflicting role.

Chang stated that the molecule’s versatility in the prostate should not come as a surprise, since the molecule’s function elsewhere depends on its location. “The effects of the androgen receptor on hair growth in men vary dramatically depending on where in the body the receptor is working,” said Chang. “When the receptor is very active in the mustache area, more hair grows. When it’s very active on the top of the skull, toward the front, hair falls out and men become bald. And the hair on the back of the head is insensitive to the receptor. The effects of hormones depend on the location.
“We found that the same is true within the cells of the prostate itself,” said Chang.

He concluded that androgen receptors work differently in different types of cells. Depending upon the role of the cell the androgen receptor will also performs different tasks. Bearing this in mind, to be effective ADT treatments need to be able to target the androgen receptors differently in different cell types. Ultimately, the goal would be to turn off the receptors in some cells while keeping it on in others. A new research challenge.

Chang’s team included researchers Yuanjie Niu; Saleh Altuwaijri; Kuo-Pao Lai; Chun-Te Wu; William A. Ricke, Ph.D., assistant professor of Urology; Jorge Yao; Shuyuan Yeh, Ph.D., associate professor of Urology; Shengqiang Yu; Kuang-Hsiang Chuang; Shu-Pin Huang; and Edward Messing, M.D., professor and chair of Urology. Henry Lardy of the University of Wisconsin is an author on one of the papers.

Joel T Nowak MA, MSW