Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 117-125 http://medscipublisher.com/index.php/cge 122 5.2 Development of new endocrine drugs The development of a new generation of endocrine drugs, including second-generation selective estrogen receptor degraders (SERDs) and targeted chimeric proteolytic agents (PROTACs), brings hope for solving the problem of drug resistance in breast cancer (Hubalek et al., 2012). These drugs are specifically designed to break down or inhibit estrogen receptors more effectively. Even if ESR1 mutations or other changes occur in cancer cells, leading to resistance to traditional therapies, they can still function (Sahin et al., 2021). Now, the second-generation serd and PROTACs are undergoing clinical trials. Early results indicate that for those patients who do not respond well to standard endocrine therapy, these new drugs have better efficacy and may also overcome the problem of drug resistance. These new drugs can also be used in combination with other targeted therapy methods to further enhance the therapeutic effect of endocrine-resistant breast cancer (Sahin et al., 2021). 5.3 Application of precision medicine and predictive biomarkers The adoption of precision medicine methods and the use of predictive biomarkers such as circulating tumor DNA (ctDNA) detection and genetic testing have become increasingly important in guiding the treatment of endocrine-resistant breast cancer. These detection methods can identify specific genetic changes that cause drug resistance in cancer cells (such as ESR1 mutations and PIK3CAmutations), thus enabling the formulation of more personalized and effective treatment plans (Ziauddin et al., 2014; Hanker et al., 2020; Sahin et al., 2021). In clinical treatment, making treatment decisions based on the results of biomarker detection can not only screen out patients who are most suitable for treatment with targeted drugs and new drugs, but also monitor whether cancer cells have developed new drug resistance. The ongoing research aims to optimize these methods, detect drug resistance problems earlier, arrange the treatment sequence reasonably, and maximize the therapeutic effect of patients with hormone receptor-positive breast cancer (Ziauddin et al., 2014; Hanker et al., 2020; Sahin et al., 2021). 6 Future Outlook 6.1 Further molecular research is conducted to determine new therapeutic targets The ongoing molecular research is crucial for clarifying the new causes of endocrine resistance in breast cancer, such as intracellular gene mutations, changes in gene expression regulation, and alterations in the surrounding environment of the tumor (Hanker et al., 2020). After researchers gain an in-depth understanding of these complex processes of action, they can find new therapeutic entry points, such as the pathways of signal transmission in the endoplasmic reticulum, the regulatory mechanisms of cell division, and the pathways by which cells cope with stress (Tyson et al., 2015; Sahin et al., 2021; Sharma et al., 2021). In animal and laboratory cell experiments, researchers have been studying some innovative drugs, such as partial agonists of estrogen receptors, PROTACs, AKT inhibitors and histone deacetylase inhibitors, etc. Some of these drugs are being used alone or in combination with endocrine therapy for clinical trials. Further in-depth molecular research is highly necessary for the development of more effective and durable treatment methods for endocrine-resistant breast cancer (Sharma et al., 2021). 6.2 Progress in individualized treatment and multi-omics strategies The development direction of breast cancer treatment is personalized treatment, that is, by using multiple omics technologies such as genomics, transcriptomics and proteomics, to formulate treatment plans based on the unique characteristics of each patient's tumor. Through these methods, rare gene mutations, changes in gene arrangement and other molecular alterations that may cause drug resistance can be discovered, thereby achieving more precise and effective treatment (Desai and Haque, 2019; Tanwar et al., 2025). Combining the data from multi-omics studies with the clinical information of patients can help identify biomarkers that predict therapeutic effects, guide the selection of targeted therapeutic drugs, improve therapeutic effects, and also reduce unnecessary drug side effects (Desai and Haque, 2019; Tanwar et al., 2025). With the increasing popularity of these technologies, personalized treatment will play a greater role in dealing with endocrine-resistant breast cancer.
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