How long does it take to become resistant to enzalutamide/enzalutamide?

The next-generation hormonal drug enzalutamide/enzalutamide has been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC), both after and before treatment with docetaxel (predocetaxel), because of its significant improvement in overall survival. Enzalutamidehas also shown impressive results in the treatment of non-metastaticCRPC in men. But not allCRPC patients respond to enzalutamide, and even for patients who respond, their benefits are limited by the development of drug resistance.

Enzalutamideis an oral androgen receptor (AR) inhibitor with 8-fold higher affinity for its target than bicalutamide. Unlike bicalutamide, which acts only at the receptor level, enzalutamide also prevents AR nuclear translocation, DNA binding, and coactivator recruitment. Adaptive resistance to enzalutamide treatment in metastatic prostate cancer may be due to activation of AR-dependent pathways (expression of constitutively active AR splice variants, AR point mutations, gene amplification and overexpression) and AR signaling-independent mechanisms (altered steroidogenesis, glucocorticoid receptor upregulation, epithelial-to-mesenchymal transition, neuroendocrine transition, autophagy, and immune system activation).

Most patients respond positively to enzalutamide when first given. However, over time, some patients may develop resistance. Drug resistance means that enzalutamide's inhibitory effect on cancer cells is reduced, resulting in the drug losing its efficacy. The rate at which resistance develops varies from person to person. Some patients may develop resistance within months, while others may maintain a longer-lasting response to the drug.

The development of resistance does not mean that enzalutamide is no longer effective. When a patient becomes resistant, doctors may consider adjusting treatment, such as using other drugs in combination or switching to a different treatment. This may improve treatment efficacy and delay the development of resistance to enzalutamide.