Hsp90 inhibitors could improve aggressive, resistant prostate cancer treatment.
A recent study suggests that men with aggressive, treatment-resistant prostate cancer could benefit from a new class of cancer drugs that overcome this resistance.
Hsp90 inhibitors target and deactivate a mechanism typically used by prostate cancer cells to become resistant to standard treatment. According to a study published in Cancer Research, Hsp90 inhibitors countered the effect of malfunctions in the androgen receptor to weaken proteins needed for the growth and survival of cancer cells.
Researchers also found that Hsp90 inhibitors stopped production of mutated forms of the androgen receptors, which removed the cancer cell’s defense against treatment.
Because these tumors need androgens to grow, blocking androgen receptors can be a successful treatment, however, cancer cells can create abnormal forms of the androgen receptor that can be switched on without hormone stimulation. Researchers studied how Hsp90 inhibitors worked with the androgen receptor variant, AR-V7, in mouse models.
Investigators found that Hsp90 inhibitors reduced levels of the normal androgen receptor and prostate cancer molecules AKT and GR.
"We call Hsp90 inhibitors 'network drugs' because they tackle several of the signals that are hijacked in cancer all at once, across a network rather than just a single signaling pathway. These drugs can hit cancer harder than those targeting only one protein, and look promising for preventing or overcoming drug resistance. Our study has found that Hsp90 inhibition can specifically stop resistance to hormone treatments in prostate cancer, through a completely new mechanism of action involving the processing of messenger RNA,” concluded study co-author, Paul Workman, FMedSci, FRS. "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."