酸性肿瘤微环境和新兴的癌症治疗策略。

IF 2.8 4区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Yongzhi Zhuang, Liquan Tong, Xueying Sun
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引用次数: 0

摘要

低氧和酸性是肿瘤微环境(TMEs)的两种不同特性。肿瘤酸度最初被认为是缺氧的“副产物”,由血管异常和过度的氧气需求引起。目前认识到,酸性在TMEs中具有独特的功能,它可以加剧异常的细胞能量代谢,抑制细胞致癌物代谢,阻碍DNA损伤修复机制,抑制免疫细胞活化,在癌变过程中发挥重要作用。酸性TMEs也是肿瘤细胞侵袭和转移的主要贡献者,并参与对包括免疫治疗在内的癌症治疗的耐药性机制。因此,开发针对酸性TMEs的新型抗癌药物可能具有相当大的临床效益。本文综述了这一快速发展领域的最新信息,包括酸性TMEs对癌症进展的影响、对当前治疗的耐药性和抗癌免疫,以及它们与缺氧和有氧糖酵解的关系。综述了导致酸性TMEs的关键分子,重点介绍了针对肿瘤酸性的抗癌药物的发展,主要是碳酸酐酶抑制剂、单羧酸转运体、液泡型腺苷三磷酸酶(v - atp酶)和Na+/H+交换物。目前,除了针对v - atp酶的质子泵抑制剂外,没有一种靶向酸性TMEs的抑制剂被批准用于临床癌症治疗。高特异性药物的开发和更敏感和精确的生物标志物的发现可能有助于提高这些抑制剂在癌症治疗中的有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Acidic Tumor Microenvironments and Emerging Therapeutic Strategies for Cancer Therapy.

Hypoxia and acidity represent two distinct properties of tumor microenvironments (TMEs). Tumor acidity was initially proposed to be a "by-product" of hypoxia, which results from abnormal vasculature and excessive oxygen demands. It is now recognized that acidity has its unique function in TMEs, as it can exacerbate abnormal cellular energy metabolism, inhibit cellular carcinogen metabolism, impede DNA damage repair mechanisms, and suppress immune cell activation, all of which play crucial roles during carcinogenesis. Acidic TMEs are also major contributors to the invasion and metastasis of tumor cells, and participate in the mechanisms underlying resistance to cancer treatments including immunotherapy. Therefore, the development of novel anti-cancer agents that target acidic TMEs may have considerable clinical benefits. This article reviews the updated information in this rapidly growing field, including the influence of acidic TMEs on cancer progression, resistance to current treatments and anti-cancer immunity, and their association with hypoxia and aerobic glycolysis. It also summarizes the key molecules that contribute to acidic TMEs and highlights the development of anti-cancer agents targeting tumor acidity, primarily inhibitors of carbonic anhydrases, monocarboxylic acid transporters, vacuolar-type adenosine triphosphatase (V-ATPase), and Na+/H+ exchangers. At present, none of the inhibitors targeting acidic TMEs have been approved for clinical use in cancer treatment, except for proton pump inhibitors that target V-ATPase. Development of highly specific agents and the discovery of more sensitive and precise biomarkers may help improve the effectiveness of these inhibitors for cancer therapy.

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来源期刊
Yonsei Medical Journal
Yonsei Medical Journal 医学-医学:内科
CiteScore
4.50
自引率
0.00%
发文量
167
审稿时长
3 months
期刊介绍: The goal of the Yonsei Medical Journal (YMJ) is to publish high quality manuscripts dedicated to clinical or basic research. Any authors affiliated with an accredited biomedical institution may submit manuscripts of original articles, review articles, case reports, brief communications, and letters to the Editor.
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