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For more than a decade, drugs that inhibit androgen receptors such as enzalutamide have been widely used in the treatment
A new study from the University of Michigan's Rogel Cancer Center suggests that androgen receptor inhibitors can fundamentally reshape the function of prostate tumors, in some cases even making them more aggressive
Androgen receptors act as engines of prostate cancer cells, while androgens act as fuel, turning on androgen receptors
Dr Joshi Alumkal, Professor of Internal Medicine at Rogel Cancer Center, said: "At the moment we need to understand how tumors become resistant to androgen receptor-targeting drugs so that we can determine how to better treat patients whose
Alumkal wanted to know what happened when these tumors first appeared, and what happened
The research team recruited prostate cancer patients for longitudinal studies to take biopsy samples
To understand drug resistance, researchers often take samples
Alumkal's continuous sampling method provides a clearer picture of how resistance to enzalumide develops
When they compared baseline samples to progression samples from the same patient, most tumors did not show significant changes in
That's not the only surprise
"We know that sometimes tumors become no longer dependent on fuel and no longer dependent on androgen receptors
But Alumkal found that in 15 percent of cases, tumors adopt another strategy
Alumkal used the car as a metaphor for this change
He found three cases of tumors that turned into double-negative prostate cancer — similar to electric cars
Although the initial tumors looked similar under the microscope, the researchers found that specific genes were expressed
Alumkal noted that the results of the continuous sampling method showed that enzalumide was improving tumor adaptation, and in some cases, the effect was remarkable
Source text search
Westbrook, T.
C.
, Guan, X.
, Rodansky, E.
et al.
Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity.
Nat Commun 13, 5345 (2022).
https://doi.
org/10.
1038/s41467-022-32701-6
