Why hormone therapy fails

Finasteride, an antiandrogen

ﾩ 2003 DIVISION OF CHEMICAL EDUCATION, AMERICAN CHEMICAL SOCIETY

The paper:

The finding:

Using gene-expression profiling, Charles Sawyers then at the University of California, Los Angeles, and collaborators found consistently elevated levels of androgen receptor mRNA in hormone therapy-resistant prostate cancer xenografts.

The surprise:

In cells with elevated androgen receptor levels, they found that the anticancer drug flips from inhibiting cell growth to stimulating it. This could potentially explain a clinical observation that some prostate cancers grow when treated with anti-androgen therapy.

The follow-up:

Using cells that express high levels of androgen receptor, Sawyers' lab is hunting for compounds that function like the current anti-androgen drugs, without stimulating growth. One of these compounds has already been licensed by a small company for preliminary testing.

Sawyers' take:

"Our experiments led to this completely serendipitous and unexpected finding about the flip from antagonist to agonist. No one would have ever guessed that. In retrospect though, it makes perfect sense."

View from the clinic:

Charles Ryan at the UCSF Comprehensive Cancer Center says: "This paper tells us that resistance to anti-androgen therapy is more complicated than we previously thought." He adds, "It hasn't changed how I practice medicine, but it is one piece of the puzzle that helps us to understand how this resistance occurs."