由于代谢再编程，癌细胞表现出高速的糖酵解，导致产生大量乳酸，同时细胞外酸度也增加。质子联结的一羧酸单体运输体（MCTs）在维持这种代谢表型中至关重要，通过介导质子耦合的乳酸通量跨越细胞膜，并有助于癌细胞的pH调节。在SLC16基因家族编码的蛋白质中，MCT1和MCT4亚型在许多癌症类型中得到了最广泛的研究，并且在固体肿瘤和血液恶性肿瘤中均过度表达。与特定的生理情况类似，MCT1和MCT4也能在肿瘤微环境中介导癌细胞间以及癌细胞与间质细胞之间的乳酸交通。这种代谢合作形式是导致癌症侵袭特征（如细胞增殖、存活、血管生成、迁移、侵袭、转移、免疫耐受和治疗抵抗）的重要原因。对MCT功能和调节的日益理解为开发新型抑制剂提供了新的途径，并可预见其在临床实践中使用。本综述概述了MCT亚型在癌症中的作用，并总结了其药理靶向的最新进展，强调了新型选择性的MCT1和/或MCT4抑制剂在癌症治疗中的潜力，并预期其被纳入临床实践中。版权所有©2023 Elsevier Ltd.。

As a result of metabolic reprogramming, cancer cells display high rates of glycolysis, causing an excess production of lactate along with an increase in extracellular acidity. Proton-linked monocarboxylate transporters (MCTs) are crucial in the maintenance of this metabolic phenotype, by mediating the proton-coupled lactate flux across cell membranes, also contributing to cancer cell pH regulation. Among the proteins codified by the SLC16 gene family, MCT1 and MCT4 isoforms are the most explored in cancers, being overexpressed in many cancer types, from solid tumours to haematological malignancies. Similarly to what occurs in particular physiological settings, MCT1 and MCT4 are able to mediate lactate shuttles among cancer cells, and also between cancer and stromal cells in the tumour microenvironment. This form of metabolic cooperation is responsible for important cancer aggressiveness features, such as cell proliferation, survival, angiogenesis, migration, invasion, metastasis, immune tolerance and therapy resistance. The growing understanding of MCT functions and regulation is offering a new path to the design of novel inhibitors that can be foreseen in clinical practices. This review provides an overview of the role of MCT isoforms in cancer and summarizes the recent advances in their pharmacological targeting, highlighting the potential of new potent and selective MCT1 and/or MCT4 inhibitors in cancer therapeutics, and anticipating its inclusion in clinical practice.Copyright © 2023 Elsevier Ltd. All rights reserved.