A new class of drug that attacks cancer indirectly - by destabilizing proteins that cancer cells need to survive and multiply - shows promise in fighting prostate cancers that have become resistant to treatment and have started spreading to other parts of the body.

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The researchers believe their findings reveal the new drugs - shown here working against prostate cancer cells - could be used to treat men with prostate cancers that have become resistant to standard treatment.
Image credit: Prof. Johann de Bono/ICR

Research in mice shows that the new drugs - called Hsp90 inhibitors - target and disable a mechanism that helps prostate cancer cells evade the effect of standard treatment.

The study - led by The Institute of Cancer Research (ICR), London, United Kingdom, and published in the journal Cancer Research - reveals important insights into the role of Hsp90 and similar proteins in drug-resistant prostate cancers, suggesting new cancer treatments may arise from discovering ways to block them.

The findings suggest the new drugs may benefit men with prostate cancer who have run out of treatment options.

Prof. Paul Workman, chief executive of the ICR and co-leader of the study, says they call the new drugs "network drugs" because they target a network of signals that cancer cells hijack, rather than just one pathway. He adds:

"These drugs can hit cancer harder than those targeting only one protein and look promising for preventing or overcoming drug resistance."

Prostate cancer cells need male hormones called androgens to feed their growth and spread. Blocking androgen receptors can be an effective treatment that cuts off their supply.

'New and unexpected mechanism of action'

In their new study, the team found Hsp90 inhibitors also appear to block production of abnormal versions of the androgen receptor, which is how cancer cells evade standard treatments that target the normal version. They produce abnormal versions of the receptor that do not require the hormone to be active.

In tests on mice injected with lab-grown human cancer cells, the team showed that Hsp90 inhibition was effective against AR-V7 - the most common androgen receptor variant.

The researchers found the drug worked in a new and unexpected way to reduce AR-V7 production. It interfered with messenger RNA - the molecules that carry the genetic code for producing the protein from DNA to the protein-making machinery in cells.

They also found that Hsp90 inhibitors reduced levels of normal androgen receptors and two other molecules necessary for prostate cancer growth: AKT and GR.

Hsp90 inhibitors are already being tested for human use in clinical trials for several types of cancer.

"It's an exciting discovery which adds a string to the bow of these cancer drugs, and means they could work against prostate cancers that have otherwise stopped responding to treatment."

Prof. Workman

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