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靶向肿瘤微环境,一种前列腺癌的新治疗方法。

Targeting the tumor microenvironment, a new therapeutic approach for prostate cancer.

作者信息

Fang Bangwei, Lu Ying, Li Xiaomeng, Wei Yu, Ye Dingwei, Wei Gonghong, Zhu Yao

机构信息

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Prostate Cancer Prostatic Dis. 2024 Apr 2. doi: 10.1038/s41391-024-00825-z.

Abstract

BACKGROUND

A growing number of studies have shown that in addition to adaptive immune cells such as CD8 + T cells and CD4 + T cells, various other cellular components within prostate cancer (PCa) tumor microenvironment (TME), mainly tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs), have been increasingly recognized as important modulators of tumor progression and promising therapeutic targets.

OBJECTIVE

In this review, we aim to delineate the mechanisms by which TAMs, CAFs and MDSCs interact with PCa cells in the TME, summarize the therapeutic advancements targeting these cells and discuss potential new therapeutic avenues.

METHODS

We searched PubMed for relevant studies published through December 10 2023 on TAMs, CAFs and MDSCs in PCa.

RESULTS

TAMs, CAFs and MDSCs play a critical role in the tumorigenesis, progression, and metastasis of PCa. Moreover, they substantially mediate therapeutic resistance against conventional treatments including anti-androgen therapy, chemotherapy, and immunotherapy. Therapeutic interventions targeting these cellular components have demonstrated promising effects in preclinical models and several clinical trials for PCa, when administrated alone, or combined with other anti-cancer therapies. However, the lack of reliable biomarkers for patient selection and incomplete understanding of the mechanisms underlying the interactions between these cellular components and PCa cells hinder their clinical translation and utility.

CONCLUSION

New therapeutic strategies targeting TAMs, CAFs, and MDSCs in PCa hold promising prospects. Future research endeavors should focus on a more comprehensive exploration of the specific mechanisms by which these cells contribute to PCa, aiming to identify additional drug targets and conduct more clinical trials to validate the safety and efficacy of these treatment strategies.

摘要

背景

越来越多的研究表明,除了CD8 + T细胞和CD4 + T细胞等适应性免疫细胞外,前列腺癌(PCa)肿瘤微环境(TME)中的各种其他细胞成分,主要是肿瘤相关巨噬细胞(TAM)、癌症相关成纤维细胞(CAF)和髓系来源的抑制细胞(MDSC),已越来越被认为是肿瘤进展的重要调节因子和有前景的治疗靶点。

目的

在本综述中,我们旨在阐述TAM、CAF和MDSC在TME中与PCa细胞相互作用的机制,总结针对这些细胞的治疗进展,并讨论潜在的新治疗途径。

方法

我们在PubMed上搜索了截至2023年12月10日发表的关于PCa中TAM、CAF和MDSC的相关研究。

结果

TAM、CAF和MDSC在PCa的肿瘤发生、进展和转移中起关键作用。此外,它们还显著介导对包括抗雄激素治疗、化疗和免疫治疗在内的传统治疗的耐药性。针对这些细胞成分的治疗干预在单独给药或与其他抗癌疗法联合使用时,已在PCa的临床前模型和一些临床试验中显示出有前景的效果。然而,缺乏用于患者选择的可靠生物标志物以及对这些细胞成分与PCa细胞之间相互作用的潜在机制的不完全理解,阻碍了它们的临床转化和应用。

结论

针对PCa中TAM、CAF和MDSC的新治疗策略具有广阔前景。未来的研究应集中在更全面地探索这些细胞促进PCa的具体机制,旨在识别更多药物靶点并进行更多临床试验以验证这些治疗策略的安全性和有效性。

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