A new class of medicine that attacks cancer indirectly by de-stabilizing proteins that cancer cells require to survive and reproduce – reveals promise in battling prostate cancers that have become tolerant to therapy and have started spreading to other areas of the body.
Study in mice reveals that the new medicines – known as Hsp90 inhibitors – target and disable a mechanism that allows prostate cancer cells evade the impact of standard therapy.
The research – led by The Institute of Cancer Research (ICR), London and presented in the journal Cancer Research – shows essential insights into the role of Hsp90 and similar proteins in drug resistant prostate cancers, indicating new cancer therapies may occur from finding ways to block them.
The results recommend the new medicines may advantage men with prostate cancer who have run out of therapy choices.
Prof. Paul Workman, chief executive of the ICR and co-leader of the research, states that they call the new medicines “network drugs” because they targeted a network of signals that cancer cells hijack, instead of just one pathway. He adds:
“These medicines can hit cancer harder than those focusing on only one protein and look ensuring for preventing or beating drug resistance.”
Prostate cancer cells require male hormones known as androgens to feed their development and spread. Preventing androgen receptors can be an efficient therapy that cuts off their supply.
‘New and surprising mechanism of action’
In their new research, the team identified Hsp90 inhibitors also seem to block production of abnormal versions of the androgen receptor, which is how cancer cells avoid standard therapies that focus on the normal version. They generate abnormal types of the receptor that do not need the hormone to be active.
In the assessments on mice injected with laboratory grown human cancer cells, the research team revealed that Hsp90 inhibition was efficient against AR-V7 – the very common androgen receptor variant.
The investigators identified the drug worked well in a new and surprising way to decrease AR-V7 production. It interrupted with messenger RNA – the molecules that carry the genetic code for generating the protein from DNA to the protein making machinery in cells.
They also identified that Hsp90 inhibitors decreased levels of normal androgen receptors and two other molecules essential for prostate cancer development: AKT and GR.
Hsp90 inhibitors are currently being tested for human use in clinical studies for several kinds of cancer.
Prof. Workman concludes saying ,
“It’s an interesting discovery which adds a string to the bow of these cancer medicines, and means they could work towards prostate cancers that have otherwise stopped reacting to therapy.”