Expanding horizons in overcoming therapeutic resistance in castration-resistant prostate cancer: targeting the androgen receptor-regulated tumor immune microenvironment

Cheng, Bisheng; Huang, Hai

doi:10.20892/j.issn.2095-3941.2023.0256

Cited by 3 publications

(2 citation statements)

References 20 publications

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“…The immune microenvironment encompasses immune cells, and variations in their infiltration levels can suggest different therapeutic outcomes, particularly in immunotherapy 11,29 . Cancer immunotherapy has revolutionized the treatment paradigms for cancer by specifically targeting the immune system to modulate anti‐tumor immunity 30 .…”

Section: Discussionmentioning

confidence: 99%

“…However, many tumors do not respond well or do not respond at all to ICIs, The main reason is the lack of tumor infiltrating lymphocytes, which significantly restricts the use of ICIs drugs. Therefore, it is necessary to study efficient treatment methods to transform immune “cold” tumors into “hot” tumors with high sensitivity to ICIs, which is also the focus of current research in this field 11–15 . A large number of experimental studies have found that the ferroptosis pathway is important in regulating the microenvironment of immunosuppressive tumors, and is closely related to the efficacy of cancer.…”

Section: Introductionmentioning

confidence: 99%

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MT1G, an emerging ferroptosis‐related gene: A novel prognostic biomarker and indicator of immunotherapy sensitivity in prostate cancer

Cheng,

Lai,

Huang

et al. 2023

Environmental Toxicology

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BackgroundProstate cancer is a leading cause of cancer‐related deaths in men worldwide. Despite advances in treatment strategies, there is still a need for novel therapeutic targets and approaches. Ferroptosis has emerged as a critical process in the development and progression of several cancers, including prostate cancer (PCA). In this study, we investigate the role of MT1G, a gene implicated in immune responses and ferroptosis, in the pathogenesis of PCA. Our objective is to elucidate its prognostic significance and its impact on the tumor microenvironment, while exploring its potential in enhancing the sensitivity to immune checkpoint inhibitor (ICI) therapy.MethodsWe utilized a combination of in silico analysis and experimental techniques to investigate the role of MT1G in PCA. First, we analyzed large‐scale genomic datasets to assess the expression pattern and prognostic significance of MT1G in PCA patients. Subsequently, we performed functional assays to explore the impact of MT1G in PCA and its potential involvement in modulating immune responses. In addition, we conducted in vivo experiments to evaluate the effect of MT1G on tumor growth and response to ICI therapy.ResultsOur analysis revealed that MT1G expression is significantly downregulated in PCA tissues compared to normal prostate tissues and is associated with poor prognosis. Furthermore, MT1G overexpression inhibited the growth of PCA cells in vitro and in vivo. Importantly, we found that MT1G regulates the tumor microenvironment by modulating immune cell infiltration and inhibiting immunosuppressive factors. Furthermore, our study reveals a significant correlation between MT1G expression levels and the response to immune checkpoint inhibitor (ICI) therapy in prostate cancer (PCA) patients, as MT1G upregulation leads to an increase in PDL‐1 expression. These findings underscore the potential of MT1G as a promising predictive biomarker for ICI therapy response in PCA patients.ConclusionOur study elucidates the pivotal role played by MT1G in the pathogenesis of prostate cancer (PCA) and its profound implications for prognosis. Moreover, it raises the intriguing possibility that MT1G could pave the way for novel therapeutic approaches in PCA treatment. This potential arises from its ability to orchestrate immune infiltration within the tumor microenvironment, consequently enhancing sensitivity to immune checkpoint inhibitor (ICI) therapy. Therefore, our findings hold substantial promise for advancing our comprehension of PCA and exploring innovative therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MT1G, an emerging ferroptosis‐related gene: A novel prognostic biomarker and indicator of immunotherapy sensitivity in prostate cancer

Cheng,

Lai,

Huang

et al. 2023

Environmental Toxicology

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Synergistic Strategies for Castration-Resistant Prostate Cancer: Targeting AR-V7, Exploring Natural Compounds, and Optimizing FDA-Approved Therapies

Rahman,

Akter,

Ahmed

et al. 2024

Cancers

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Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge due to its resistance to standard androgen deprivation therapy (ADT). The emergence of androgen receptor splice variant 7 (AR-V7) has been implicated in CRPC progression, contributing to treatment resistance. Current treatments, including first-generation chemotherapy, androgen receptor blockers, radiation therapy, immune therapy, and PARP inhibitors, often come with substantial side effects and limited efficacy. Natural compounds, particularly those derived from herbal medicine, have garnered increasing interest as adjunctive therapeutic agents against CRPC. This review explores the role of AR-V7 in CRPC and highlights the promising benefits of natural compounds as complementary treatments to conventional drugs in reducing CRPC and overcoming therapeutic resistance. We delve into the mechanisms of action underlying the anti-CRPC effects of natural compounds, showcasing their potential to enhance therapeutic outcomes while mitigating the side effects associated with conventional therapies. The exploration of natural compounds offers promising avenues for developing novel treatment strategies that enhance therapeutic outcomes and reduce the adverse effects of conventional CRPC therapies. These compounds provide a safer, more effective approach to managing CRPC, representing a significant advancement in improving patient care.

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Myeloid-Derived Suppressor Cells and Macrophage Polarization in Cancer Immunotherapy

Hosseini,

Akbarzadeh,

Jadidi-Niaragh

2024

Advances in Medical Diagnosis, Treatment, and Care

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Myeloid-derived suppressor cells (MDSCs) and macrophage polarization are key functional components of the immune system in shaping the tumor microenvironment (TME) and modulating immune responses. MDSCs, characterized by their heterogeneity and potent immunosuppressive functions, negatively affect anti-tumor immunity by inhibiting T cell activation, promoting regulatory T cell (Treg) expansion, and enhancing tumor growth and metastasis. Similarly, macrophage polarization into M1 (classically activated) and M2 (alternatively activated) phenotypes significantly influences tumor progression, with M2 macrophages facilitating immunosuppression, angiogenesis, and tissue remodeling. Therapeutic strategies targeting these cells focus on depleting MDSCs, reprogramming macrophages from the M2 to M1 phenotype, and disrupting their recruitment and activation signals within the TME. This chapter explores the complex biology of MDSCs and polarized macrophages, their interactions within the TME, their impact on cancer progression and treatment outcomes, and the future landscape of this field.

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Expanding horizons in overcoming therapeutic resistance in castration-resistant prostate cancer: targeting the androgen receptor-regulated tumor immune microenvironment

Cited by 3 publications

References 20 publications

MT1G, an emerging ferroptosis‐related gene: A novel prognostic biomarker and indicator of immunotherapy sensitivity in prostate cancer

MT1G, an emerging ferroptosis‐related gene: A novel prognostic biomarker and indicator of immunotherapy sensitivity in prostate cancer

Synergistic Strategies for Castration-Resistant Prostate Cancer: Targeting AR-V7, Exploring Natural Compounds, and Optimizing FDA-Approved Therapies

Myeloid-Derived Suppressor Cells and Macrophage Polarization in Cancer Immunotherapy

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