An important feature shared by many cancer cells is drastically altered metabolism that is critical for rapid growth and proliferation. The distinctly reprogrammed metabolism in cancer cells makes it possible to manipulate the levels of metabolites for cancer treatment. Citrate is a key metabolite that bridges many important metabolic pathways. Recent studies indicate that manipulating the level of citrate can impact the behaviors of both cancer and immune cells, resulting in induction of cancer cell apoptosis, boosting immune responses, and enhanced cancer immunotherapy. In this review, we discuss the recent developments in this emerging area of targeting citrate in cancer treatment. Specifically, we summarize the molecular basis of altered citrate metabolism in both tumors and immune cells, explore the seemingly conflicted growth promoting and growth inhibiting roles of citrate in various tumors, discuss the use of citrate in the clinic as a novel biomarker for cancer progression and outcomes, and highlight the new development of combining citrate with other therapeutic strategies in cancer therapy. An improved understanding of complex roles of citrate in the suppressive tumor microenvironment should open new avenues for cancer therapy.

中文翻译：

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靶向柠檬酸盐作为癌症治疗的新治疗策略。

许多癌细胞共有的一个重要特征是新陈代谢发生了巨大变化，这对于快速生长和增殖至关重要。癌细胞中明显重新编程的代谢使控制代谢物水平用于癌症治疗成为可能。柠檬酸盐是连接许多重要代谢途径的关键代谢物。最近的研究表明，控制柠檬酸盐的水平可以影响癌细胞和免疫细胞的行为，从而诱导癌细胞凋亡、增强免疫反应和增强癌症免疫治疗。在这篇综述中，我们讨论了在癌症治疗中靶向柠檬酸盐这一新兴领域的最新进展。具体来说，我们总结了肿瘤和免疫细胞中柠檬酸盐代谢改变的分子基础，探讨柠檬酸盐在各种肿瘤中看似矛盾的生长促进和生长抑制作用，讨论柠檬酸盐在临床中作为癌症进展和结果的新型生物标志物的用途，并强调将柠檬酸盐与其他治疗策略相结合在癌症治疗中的新发展。更好地理解柠檬酸盐在抑制性肿瘤微环境中的复杂作用应该为癌症治疗开辟新途径。