Driven by therapeutic drugs, tumors have changed from fuel vehicles to electric vehicles

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