Major Research Findings

Enzalutamide is an androgen receptor (AR) inhibitor used to treat castration-resistant prostate cancer (CRPC). Several studies have evaluated the efficacy and safety of enzalutamide, examining its effects, side effects, and optimal administration.

One study found that elevating SOX2 increased the expression of neuroendocrine markers but did not reduce the inhibitory effects of enzalutamide. 7 Another study reported that abiraterone and enzalutamide may have different adverse effects on the cardiovascular system. 6 Furthermore, enzalutamide and abiraterone have been shown to have similar effects on delaying bone progression and improving bone-related outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). 12 A combination of tautomycin and enzalutamide has been shown to synergistically inhibit cell proliferation and AR signaling in CRPC cells. 3 Additionally, simvastatin and enzalutamide have been shown to exert additive growth inhibition in androgen-sensitive prostate cancer cells, accompanied by strong induction of autophagy. 14 Furthermore, studies have investigated factors that predict the efficacy and adverse effects of enzalutamide in patients. 15

A combination of orlistat and enzalutamide has been found to suppress tumor growth in a PC3 tumor-bearing mouse model through inhibition of fatty acid synthase (FASN). 5 A novel molecule, PAWI-2, has been reported to inhibit the proliferation of androgen-sensitive and androgen-insensitive prostate cancer cells and synergize with enzalutamide to inhibit the growth of CRPC cells. 8 Enzalutamide has been shown to affect health-related quality of life (HRQoL) in patients with metastatic CRPC. 13 Enzalutamide monotherapy may affect multiparametric 3T magnetic resonance imaging (MRI) of prostate cancer, leading to tumor size reduction, downstaging, and an increase in ADC values. 16 A combination of IU1 and enzalutamide has been shown to synergistically inhibit AR signaling in CRPC cells. 1 Inhibiting the feedback loop between neuroendocrine differentiation and macrophages has been found to improve the therapeutic effects of enzalutamide. 10 LOX-1 activation by oxLDL may induce AR and AR-V7 expression via NF-κB and STAT3 signaling pathways, reducing enzalutamide cytotoxicity. 2 A meta-analysis revealed that abiraterone and enzalutamide have different side effect profiles in patients with mCRPC. 11 Adding standard enzalutamide medication may have synergistic effects on the response to [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy in mCRPC patients. 4 An AKR1C3 inhibitor, KV-37, exhibits antineoplastic effects and potentiates enzalutamide in combination therapy in prostate adenocarcinoma cells. 9

Benefits and Risks

Benefits Summary

Enzalutamide has shown benefits in the treatment of CRPC, including prolonged survival, tumor growth inhibition, and delayed bone-related events. Some studies have suggested that enzalutamide may enhance treatment effects by inhibiting neuroendocrine differentiation and controlling macrophage activation. 10 3 9

Risks Summary

Enzalutamide has been reported to have risks of cardiovascular side effects, bone-related events, fatigue, and rash. Enzalutamide may also enhance side effects when used in combination with other drugs, so caution is necessary. 6 11

Comparison Across Studies

Commonalities

Many studies have evaluated the efficacy and safety of enzalutamide, aiming to understand its effects on CRPC patients. Some studies have examined different administration methods and combination therapies for enzalutamide. Additionally, efforts have been made to minimize the side effects associated with enzalutamide.

Differences

Research on the effects and side effects of enzalutamide has varying results due to differences in the study population, design, and assessment indicators. Studies on enzalutamide administration methods and combination therapies may use different drugs and combinations, making it difficult to compare results.

Consistency and Contradictions of Results

Studies on the effects of enzalutamide have shown consistent results. However, there is variability in side effect reports across studies. This may be due to differences in the study population or design. It can also be challenging to compare results from studies on enzalutamide administration methods and combination therapies.

Implications for Everyday Life and Considerations

While enzalutamide is an effective drug for CRPC treatment, it is important to consider the risks of side effects. Enzalutamide administration should be done carefully under the guidance of a physician. Combination therapies involving enzalutamide should be discussed with a doctor.

Limitations of Current Research

Studies on the effects of enzalutamide may not have fully evaluated long-term effects or side effects. Studies on enzalutamide administration methods and combination therapies may have limited study populations. Furthermore, studies identifying factors predicting enzalutamide efficacy and side effects may not have adequately validated their predictive capabilities.

Future Directions for Research

Research is needed to evaluate the long-term effects and side effects of enzalutamide. Studies on enzalutamide administration methods and combination therapies should be conducted with larger and more diverse patient populations. Additionally, identifying and validating factors that predict enzalutamide efficacy and side effects using more precise methods is crucial.

Conclusion

Enzalutamide is an effective drug for CRPC treatment, offering benefits such as prolonged survival, tumor growth inhibition, and delayed bone-related events. However, it has also been reported to have risks such as cardiovascular side effects, bone-related events, fatigue, and rash. Enzalutamide administration should be done carefully under the guidance of a physician. Future research should evaluate long-term effects and side effects and identify factors that predict enzalutamide efficacy and side effects.