A candidate drug, which acts in a novel way, has shown promising results in the laboratory against advanced prostate cancer that was insensitive to reduced levels of male sex hormones, according to a paper published in Nature Communications journal.

Prostate cancers initially tend to be sensitive to male sex hormones, known as androgens. Treatment to reduce androgen levels, either with drugs or surgically, can inhibit the growth of such cancers. However, prostate cancers can become insensitive to androgen levels. There are limited treatment options for such ‘castration-resistant prostate cancer.’

The ‘androgen receptor’, a molecule found inside cells, has a critical role in the development and progression of prostate cancer. When androgens bind to the receptor, it became activated and set off a process that allowed cancer cells to proliferate. In late stages of the disease, the receptor could be in a permanently activated state.

However, the androgen receptor does not act alone – it needs help from a protein known as PELP1.

Ganesh V. Raj, a urologic cancer surgeon at the University of Texas Southwestern Medical Center at Dallas in the U.S., and his colleagues have designed a small protein-like molecule that could block the androgen receptor’s interaction with PELP1.

In the Nature Communications paper, they reported that the molecule, D2, was able to prevent tumour growth in a mouse prostate cancer model. Current treatment options for advanced prostate cancers targeted either the production of androgen or the androgen receptor where the androgen binds, observed Dr. Raj in email. These methods did not work for a long as the prostate cancer then evolved mechanisms of resistance, either by producing more androgen or changing the receptor so that it was no longer responsive to the drugs.

“The drug we created, D2, blocks the androgen receptor in a fundamentally different manner and prevents the androgen receptor from functioning even if androgen is present,” he pointed out.

“D2 is in advanced pre-clinical testing and we hope will make it to clinical trials soon,” he added.

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