Combination of molecular-targeted drugs with endocrine therapy for hormone-resistant breast cancer

Area of Science:

• Oncology
• Endocrinology
• Pharmacology

Background:

• Estrogen receptor (ER)-positive breast cancer often develops resistance to endocrine therapy.
• Overcoming this resistance is a major focus in breast cancer research.
• Current strategies involve combination therapies to restore endocrine sensitivity.

Purpose of the Study:

• To review the mechanistic principles of combining molecular-targeted drugs with endocrine therapy.
• To explore strategies for overcoming endocrine resistance in ER-positive breast cancer.
• To discuss ongoing clinical trials and novel therapeutic approaches.

Main Methods:

• Review of current literature on endocrine resistance and combination therapies.
• Analysis of mechanistic principles underlying drug interactions.
• Discussion of clinical trial data for signal pathway inhibitors, CDK4/6 inhibitors, and HDAC inhibitors.
• Application of a hybrid car model to explain therapeutic strategies.

Main Results:

• Combination therapy with mammalian target of rapamycin (mTOR) inhibitors like everolimus alongside endocrine therapy is an established option post-aromatase inhibitor progression.
• Ongoing clinical trials are evaluating various signal pathway inhibitors and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.
• Histone deacetylase (HDAC) inhibitors, such as entinostat, have shown promising results in early trials.

Conclusions:

• Combination therapy represents a key strategy to overcome endocrine resistance in ER-positive breast cancer.
• Targeted therapies, including mTOR inhibitors, CDK4/6 inhibitors, and HDAC inhibitors, are vital components of these combinations.
• Further research and clinical trials are essential to optimize these combination strategies for improved patient outcomes.