The cellular-centered view of hypoxia tumor microenvironment: Molecular mechanisms and therapeutic interventions

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-06-14 DOI:10.1016/j.bbcan.2024.189137
Tian-Qi Zhang , Qian-Yu Lv , Wei-Lin Jin
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Abstract

Cancer is a profoundly dynamic, heterogeneous and aggressive systemic ailment, with a coordinated evolution of various types of tumor niches. Hypoxia plays an indispensable role in the tumor micro-ecosystem, drastically enhancing the plasticity of cancer cells, fibroblasts and immune cells and orchestrating intercellular communication. Hypoxia-induced signals, particularly hypoxia-inducible factor-1α (HIF-1α), drive the reprogramming of genetic, transcriptional, and proteomic profiles. This leads to a spectrum of interconnected processes, including augmented survival of cancer cells, evasion of immune surveillance, metabolic reprogramming, remodeling of the extracellular matrix, and the development of resistance to conventional therapeutic modalities like radiotherapy and chemotherapy. Here, we summarize the latest research on the multifaceted effects of hypoxia, where a multitude of cellular and non-cellular elements crosstalk with each other and co-evolve in a synergistic manner. Additionally, we investigate therapeutic approaches targeting hypoxic niche, encompassing hypoxia-activated prodrugs, HIF inhibitors, nanomedicines, and combination therapies. Finally, we discuss some of the issues to be addressed and highlight the potential of emerging technologies in the treatment of cancer.

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以细胞为中心的缺氧肿瘤微环境观:分子机制和治疗干预。
癌症是一种极具动态性、异质性和侵袭性的全身性疾病,各种类型的肿瘤龛协调演化。缺氧在肿瘤微生态系统中扮演着不可或缺的角色,它极大地增强了癌细胞、成纤维细胞和免疫细胞的可塑性,并协调着细胞间的交流。缺氧诱导信号,尤其是缺氧诱导因子-1α(HIF-1α),驱动着基因、转录和蛋白质组图谱的重编程。这导致了一系列相互关联的过程,包括提高癌细胞的存活率、逃避免疫监视、新陈代谢重编程、重塑细胞外基质,以及对放疗和化疗等传统治疗方式产生抗药性。在这里,我们总结了有关缺氧的多方面影响的最新研究,在缺氧的影响下,多种细胞和非细胞因素相互交织,以协同的方式共同演化。此外,我们还研究了针对缺氧龛的治疗方法,包括缺氧激活原药、HIF 抑制剂、纳米药物和联合疗法。最后,我们讨论了一些有待解决的问题,并强调了新兴技术在治疗癌症方面的潜力。
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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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