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Published on: June 13, 2014
Targeted therapies for ER+/HER2- metastatic breast cancer
Mutsuko Yamamoto-Ibusuki1, Monica Arnedos2,3, Fabrice André4,5,6
1Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. mibusuki@kumamoto-u.ac.jp.
Abstract:
The majority of breast cancers present with estrogen receptor (ER)-positive and human epidermal growth factor receptor (HER2)-negative features and might benefit from endocrine therapy. Although endocrine therapy has notably evolved during the last decades, the invariable appearance of endocrine resistance, either primary or secondary, remains an important issue in this type of tumor. The improvement of our understanding of the cancer genome has identified some promising targets that might be responsible or linked to endocrine resistance, including alterations affecting main signaling pathways like PI3K/Akt/mTOR and CCND1/CDK4-6 as well as the identification of new ESR1 somatic mutations, leading to an array of new targeted therapies that might circumvent or prevent endocrine resistance. In this review, we have summarized the main targeted therapies that are currently being tested in ER+ breast cancer, the rationale behind them, and the new agents and combinational treatments to come.
Insights
Targeted therapies show promise in overcoming endocrine resistance in estrogen receptor-positive (ER+) breast cancer. This review highlights new agents and combinations targeting key pathways and mutations to improve treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Estrogen receptor (ER)-positive, HER2-negative breast cancer is common and often treated with endocrine therapy.
- Endocrine resistance, both primary and secondary, remains a significant challenge in managing ER+ breast cancer.
- Genomic advancements have identified key signaling pathways and mutations linked to endocrine resistance.
Purpose of the Study:
- To review current and emerging targeted therapies for ER+ breast cancer.
- To elucidate the rationale behind these targeted treatments.
- To discuss future directions in combinational therapies for endocrine resistance.
Main Methods:
- Literature review of targeted therapies in ER+ breast cancer.
- Analysis of genomic alterations driving endocrine resistance.
- Summary of ongoing clinical trials and novel agents.
Main Results:
- Targeted therapies focus on pathways like PI3K/Akt/mTOR and CCND1/CDK4-6.
- ESR1 somatic mutations are identified as targets for novel therapeutic strategies.
- New agents and combination treatments are under investigation to overcome resistance.
Conclusions:
- Targeted therapies offer a promising strategy to circumvent or prevent endocrine resistance in ER+ breast cancer.
- Understanding the molecular basis of resistance informs the development of next-generation treatments.
- Future research focuses on novel agents and combination regimens to improve patient outcomes.
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