Dual Inhibitors Target ER+ Breast Cancer Resistance

On April 9, 2025, a groundbreaking study was published in the journal RSC Medicinal Chemistry exploring novel compounds designed to combat hormone-resistant breast cancer. The research highlights the development of compounds that inhibit dual enzymes critical to estrogen production, specifically aromatase and steroid sulfatase, which may significantly enhance treatment efficacy for estrogen receptor-positive (ER+) breast cancer cases.

Background on Hormone-Receptor Positive Breast Cancer

Estrogen receptor-positive breast cancers, which account for approximately 70% of all breast cancer diagnoses, frequently develop resistance to conventional hormone therapies. As a result, novel therapeutic approaches are imperative to improve patient outcomes. This new research introduces dual aromatase-steroid sulfatase inhibitors (DASI) as a promising solution.

Innovative Compounds for Overcoming Resistance

Dr. Paul Foster from the University of Birmingham, a co-author of the study, emphasized the significance of these findings, stating:

“This is an exciting new development that could pave the way for treating the most common breast cancer when other therapies stop working.”

The study demonstrated that specific benzofuran-based molecules possess the ability to inhibit both aromatase and steroid sulfatase, providing an alternative mechanism to suppress estrogen production. This dual-targeting strategy might ultimately assist in reducing estrogen levels more effectively in ER+ breast cancer cells.

Chemical Modifications Enhance Efficacy

Previous iterations of similar compounds unfortunately targeted only a single enzyme, leading to suboptimal therapeutic effects. Remarkably, the application of a simple methyl group to these compounds resulted in the unexpected dual inhibition of both enzymes. The following table illustrates the compounds discussed in the study:

Future Directions for Research

The milestones achieved through this research pave the way for further investigations aimed at developing more potent dual inhibitors to address treatment resistance in ER+ breast cancer. Collaborators Dr. Claire Simons from the University of Cardiff and Dr. Foster are optimistic that these compounds could lead to a new class of breast cancer treatments.

Future studies will explore:

• Preclinical and clinical evaluations of the DASIs in overcoming endocrine therapy resistance.
• Optimization of chemical modifications to enhance dual inhibitory activity.
• Assessments of long-term safety and efficacy in diverse patient populations.

Conclusion

The introduction of dual aromatase-steroid sulfatase inhibitors represents a crucial advancement in the treatment of ER+ breast cancer, particularly in cases that have developed resistance to existing therapies. The intersection of chemistry and oncology offers a promising horizon for future cancer treatment and improved patient outcomes.

References

[1] Ahmed G. Eissa et al, Development of benzofuran-derived sulfamates as dual aromatase-steroid sulfatase inhibitors (DASIs): design, synthesis and biological evaluation, RSC Medicinal Chemistry (2025).

[2] Novel compounds target dual enzymes to combat hormone-resistant breast cancer (2025, April 9) retrieved 9 April 2025.