Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 306-316 http://medscipublisher.com/index.php/cge 313 cyclin-dependent kinase (CDK)12, enhancer of Zeste homolog 2 (EZH2), toll-like receptors (TLRs), and OX-40 (CD134) have shown potential in overcoming resistance mechanisms and enhancing anti-tumor immune responses (Omar and Tolba, 2019). These novel targets could provide additional pathways to modulate the immune system and improve patient outcomes. 7.2 Personalized immunotherapy The integration of multi-omics data, including genomics, transcriptomics, proteomics, and metabolomics, is essential for tailoring individualized treatment regimens (Chen, 2024). By analyzing the tumor mutational burden, immune cell infiltration, and specific biomarkers, personalized immunotherapy can be developed to enhance the efficacy of ICIs in TNBC (Thomas et al., 2021). This approach aims to identify patient-specific factors that predict response to ICIs, thereby optimizing treatment strategies and improving clinical outcomes. 7.3 Innovation in combination therapy strategies Investigating novel combination approaches involving ICIs and other modalities is a promising strategy to enhance therapeutic efficacy. Combining ICIs with chemotherapy, targeted therapies, cancer vaccines, and other immune modulatory drugs such as PARP inhibitors, MEK inhibitors, and TGF-β inhibitors has shown potential in preclinical and clinical studies (Liu et al., 2018; Cyprian et al., 2019; Majidpoor and Mortezaee, 2021; Patience et al., 2021; Guo et al., 2024). For instance, the combination of an mRNA vaccine encoding tumor antigen MUC1 with anti-CTLA-4 monoclonal antibody significantly enhanced anti-tumor immune responses in TNBC models (Liu et al., 2018). These innovative combination therapies aim to create a more favorable immune environment and potentiate the anti-tumor effects of ICIs. 7.4 Addressing equity issues Enhancing global accessibility of ICIs and conducting trials in diverse populations is critical to ensure equitable healthcare outcomes. The current landscape of clinical trials often lacks representation from diverse ethnic and socioeconomic groups, which can lead to disparities in treatment efficacy and accessibility (Thomas et al., 2021). Efforts should be made to conduct inclusive clinical trials and develop strategies to make ICIs more affordable and accessible worldwide. This includes addressing logistical, financial, and educational barriers that hinder the widespread adoption of ICIs in underrepresented populations. Acknowledgments We sincerely thank the anonymous peer reviewers for their valuable comments and constructive suggestions. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Adams S., Diamond J., Hamilton E., Pohlmann P., Tolaney S., Molinero L., Zou W., Liu B., Waterkamp D., Funke R., and Powderly J., 2016, Abstract p2-11-06: safety and clinical activity of atezolizumab (Anti-Pdl1) in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer, Cancer Research, 76(4_Supplement): P2-11-06. https://doi.org/10.1158/1538-7445.sabcs15-p2-11-06 PMID: 33568344 Ali M.A., Aiman W., Shah S.S., Hussain M., Kashyap R., 2020, Efficacy and safety of pembrolizumab based therapies in triple-negative breast cancer: a systematic review of clinical trials, Critical Reviews in Oncology/Hematology, 157: 103197. https://doi.org/10.1016/j.critrevonc.2020.103197 Blackley E., and Loi S., 2019, Targeting immune pathways in breast cancer: review of the prognostic utility of tils in early stage triple negative breast cancer (Tnbc), Breast, 48(Suppl 1): s44-s48. https://doi.org/10.1016/s0960-9776(19)31122-1 Chen S.Y., 2024, Optimizing drug therapy using genomic information: a pathway to personalized medicine, International Journal of Molecular Medical Science, 14(1): 61-68. https://doi.org/10.5376/ijmms.2024.14.0009 Cyprian F.S., Akhtar S., Gatalica Z., and Vranić S., 2019, Targeted immunotherapy with a checkpoint inhibitor in combination with chemotherapy: a new clinical paradigm in the treatment of triple-negative breast cancer, Bosnian Journal of Basic Medical Sciences, 19(3): 227-233. https://doi.org/10.17305/bjbms.2019.4204
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