Targeting autophagy in urological system cancers: From underlying mechanisms to therapeutic implications

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-10-18 DOI:10.1016/j.bbcan.2024.189196
Ziyue Yuan , Jiani He , Zhijia Li , Bo Fan , Lan Zhang , Xiaojun Man
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Abstract

The urological system, including kidneys, ureters, bladder, urethra and prostate is known to be vital for blood filtration, waste elimination and electrolyte balance. Notably, urological system cancers represent a significant portion of global cancer diagnoses and mortalities. The current therapeutic strategies for early-stage cancer primarily involve resection surgery, which significantly affects the quality of life of patients, whereas advanced-stage cancer often relies on less effective chemo- or radiotherapy. Recently, accumulating evidence has revealed that autophagy, a crucial process in which excess organelles or inclusions within cells are removed to maintain cell homeostasis, has numerous links to urological system cancers. In this review, we focus on summarizing the underlying two-sided mechanisms of autophagy in urological system cancers. We also review the current clinical drugs targeting autophagy, which demonstrate significant potential in improving treatment outcomes for urological system cancers. In addition, we provide an overview of the research status of novel small molecule compounds targeting autophagy that are in the preclinical stages of investigation. Furthermore, drug combinations based on autophagy modulation strategies in urological system cancers are systematically summarized and discussed. These findings provide comprehensive new insight for the future discovery of more autophagy-related drug candidates.

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以泌尿系统癌症中的自噬为靶点:从基本机制到治疗意义。
众所周知,泌尿系统(包括肾脏、输尿管、膀胱、尿道和前列腺)对血液过滤、废物排出和电解质平衡至关重要。值得注意的是,泌尿系统癌症占全球癌症诊断和死亡人数的很大一部分。目前对早期癌症的治疗策略主要涉及切除手术,这严重影响了患者的生活质量,而晚期癌症通常依赖于效果较差的化疗或放疗。最近,越来越多的证据表明,自噬是清除细胞内多余细胞器或内含物以维持细胞平衡的一个重要过程,它与泌尿系统癌症有许多联系。在这篇综述中,我们重点总结了泌尿系统癌症中自噬的基本双面机制。我们还回顾了目前以自噬为靶点的临床药物,这些药物在改善泌尿系统癌症的治疗效果方面表现出了巨大的潜力。此外,我们还概述了处于临床前研究阶段的以自噬为靶点的新型小分子化合物的研究现状。此外,我们还系统地总结和讨论了基于自噬调节策略的药物组合在泌尿系统癌症中的应用。这些发现为今后发现更多与自噬相关的候选药物提供了全面的新见解。
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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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