Cancer Genetics and Epigenetics, 2025, Vol.13, No.1, 21-31 http://medscipublisher.com/index.php/cge 27 Combining the characteristics of low tumor mutational burden and weak antigen presentation, a typical "cold tumor" microenvironment was formed, which greatly increased the difficulty of immunotherapy (Xu et al., 2022). This special microenvironment makes it difficult for conventional immunotherapy to break through multiple defense mechanisms. Despite the technical bottlenecks, the new immune intervention strategy still demonstrates significant application value. At present, innovative methods such as vaccine treatment and adoptive cell infusion are being adopted to activate the body's anti-tumor immunity (Xu et al., 2022). The microenvironment remodeling technology for androgen receptor signal regulation is in the research and development stage, aiming to enhance the therapeutic response of castration-resistant prostate cancer (Cheng and Huang, 2023). By systematically analyzing the interaction network between the immune escape mechanism and the tumor microenvironment (TME), it is expected to design more precise individualized treatment strategies (Kim and Cho, 2022). 7 Molecular Targeted Therapy and Precision Medicine 7.1 Research and development of targeted pathway therapeutic drugs The latest research and development of prostate cancer treatment drugs focuses on the regulatory mechanisms of core molecular pathways. Androgen receptor (AR) and the PI3K/Akt/mTOR signaling network have become important intervention targets due to their key regulatory roles in disease progression. Clinical studies have confirmed that AR antagonists and PI3K/Akt pathway inhibitors have shown significant therapeutic effects, opening up new therapeutic approaches (Ciccarese et al., 2017; Maekawae et al., 2024). PARP inhibitors targeting DNA repair defects (such as BRCA1/2 gene mutations) have significant advantages in patients with abnormal homologous recombination repair (Giunta et al., 2021; Drews et al., 2022). The clinical application of genetic testing technology has promoted the development of precision treatment. By identifying tumor-specific genetic variations (such as AR gene mutations), individualized treatment plans can be formulated. Treatment decisions based on genomic sequencing are becoming increasingly popular, enabling doctors to select the optimal therapy according to the tumor characteristics of patients (Ku et al., 2019; Mateo et al., 2021). 7.2 Combined therapy and individualized treatment strategies Multi-pathway combined treatment regimens are becoming a key means to improve therapeutic effects. By acting synchronously on different signal networks, such methods can break through the limitations of a single drug and deal with the heterogeneous characteristics of tumors. Studies have confirmed that the combination of AR blockers and PI3K/Akt inhibitors can produce cumulative benefits and significantly improve clinical outcomes (Sorrentino and Di, 2023; Maekawae et al., 2024). The combined application of PARP inhibitors and immunotherapy has shown the potential to enhance immune activity in patients with DNA repair deficiency (Ku et al., 2019; Drews et al., 2022). The precision medicine framework guides clinical practice by evaluating the genomic characteristics of tumors. For example, detecting ARgene mutations can predict the reactivity of targeted drugs, while abnormal DNA repair pathways suggest the applicability of PARP inhibitors (Giunta et al., 2021; Wikstrom et al., 2024). The integrated application of molecular detection technology has laid the foundation for the implementation of customized treatment plans (Bashraheel et al., 2020; Mateo et al., 2021). 7.3 Research on breakthrough strategies for drug resistance The research on the mechanism of drug resistance is the focus of current therapeutic breakthroughs. Regarding the drug resistance phenomenon of AR-targeted therapy, various mechanisms such as AR gene mutations, increased copy numbers and splicing variations have been discovered. The new generation of AR inhibitors can specifically act on drug-resistant variants, bringing new hope to drug-resistant patients (Ku et al., 2019; Maekawae et al., 2024). In addition to the AR-related drug resistance mechanism, the abnormal activation of the PI3K/Akt pathway has been confirmed to be associated with the phenomenon of multi-drug resistance. The development of the new
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