天冬酰胺：靶向肿瘤疗法的主要代谢结
Asparagine: A key metabolic junction in targeted tumor therapy
影响因子:10.50000
分区:医学2区 Top / 药学1区
发表日期:2024 Aug
作者:
Xuan Wang, Weijian Gong, Xueyou Xiong, Xuemei Jia, Juan Xu
摘要
肿瘤微环境中的营养生物利用度在肿瘤增殖和转移中起关键作用。在这些营养素中，谷氨酰胺是促进肿瘤生长和增殖的关键物质，其下游代谢产物天冬酰胺在肿瘤中也至关重要。研究表明，当谷氨酰胺耗尽时，肿瘤细胞可以依靠天冬酰胺来维持其生长。鉴于肿瘤细胞增殖对天冬酰胺的依赖，限制其生物利用度已成为癌症治疗中有前途的策略。例如，使用天冬酰胺酶是一种耗尽天冬酰胺的酶，它一直是急性淋巴细胞白血病的关键化学疗法之一（ALL）。然而，肿瘤细胞可以适应天冬冬酰胺限制，从而导致化疗降低，以及使不同遗传改变的肿瘤敏感或适应天冬酰胺限制的机制。我们回顾天冬酰胺的来源，并探索限制其生物利用度如何影响特定遗传改变的肿瘤的发展。希望通过针对适应天冬酰胺限制的信号通路和这些途径中的某些因素，可以解决耐药性问题。重要的是，这些策略为遗传改变的癌症提供了精确的治疗方法。
Abstract
Nutrient bioavailability in the tumor microenvironment plays a pivotal role in tumor proliferation and metastasis. Among these nutrients, glutamine is a key substance that promotes tumor growth and proliferation, and its downstream metabolite asparagine is also crucial in tumors. Studies have shown that when glutamine is exhausted, tumor cells can rely on asparagine to sustain their growth. Given the reliance of tumor cell proliferation on asparagine, restricting its bioavailability has emerged as promising strategy in cancer treatment. For instance, the use of asparaginase, an enzyme that depletes asparagine, has been one of the key chemotherapies for acute lymphoblastic leukemia (ALL). However, tumor cells can adapt to asparagine restriction, leading to reduced chemotherapy efficacy, and the mechanisms by which different genetically altered tumors are sensitized or adapted to asparagine restriction vary. We review the sources of asparagine and explore how limiting its bioavailability impacts the progression of specific genetically altered tumors. It is hoped that by targeting the signaling pathways involved in tumor adaptation to asparagine restriction and certain factors within these pathways, the issue of drug resistance can be addressed. Importantly, these strategies offer precise therapeutic approaches for genetically altered cancers.