Patients whose tumours contain a shortened protein called AR-V7 do not respond to enzalutamide and abiraterone, research has shown.
The protein is detectable in the blood, raising the possibility of a test that could help doctors plan the best form of treatment for men with advanced prostate cancer.
Enzalutamide and abiraterone work in different ways to tackle prostate cancer that has become resistant to standard hormone treatments.
In a new study, no patients who tested positive for AR-V7 responded to either drug.
A large proportion of those who lacked the protein did respond.
Enzalutamide and abiraterone have proved highly successful in extending the lives of 80 per cent of men with advanced prostate cancer. However, they do nothing for the remaining 20 per cent. Scotland was the first part of the UK to approve the use of enzalutamide on the NHS when the Scottish Medicines Consortium announced its decision on the drug last year while abiraterone has been available since 2012.
But lead scientist Dr Emmanuel Antonarakis, from Johns Hopkins University in the US, said: "Patients whose blood samples contained AR-V7 got no benefit from either enzalutamide or abiraterone.
"Until now, we haven't been able to predict which patients will not respond to these therapies."