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Updated: Apr 28, 2026
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
Monocarboxylate transporters as targets and mediators in cancer therapy response
F Baltazar1, C Pinheiro2, F Morais-Santos3
1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, and CVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. fbaltazar@ecsaude.uminho.pt.
Abstract:
Monocarboxylate transporters (MCTs) belong to a family of transporters, encoded by the SLC16 gene family, which is presently composed by 14 members, but only MCT1 to 4 have been biochemically characterized. They have important functions in healthy tissues, being involved in the transmembrane transport of lactic acid and other monocarboxylic acids in human cells. One of the recently recognized hallmarks of cancer is altered metabolism, with high rates of glucose consumption and consequent lactate production. To maintain this metabolic phenotype, cancer cells upregulate a series of plasma membrane proteins, including MCTs. MCT1 and MCT4, in particular, play a dual role in the maintenance of the metabolic phenotype of tumour cells. On one hand, they facilitate the efflux of lactate and, on the other hand, they contribute to the preservation of the intracellular pH, by co-transporting a proton. Thus, MCTs are attractive targets in cancer therapy, especially in cancers with a hyper-glycolytic and acid-resistant phenotype. Recent evidence demonstrates that MCTs are involved in cancer cell uptake of chemotherapeutic agents, including 3-bromopyruvate. In this way MCTs can act as "Trojan horses", as their elevated expression in cancer cells can mediate the entry of this chemotherapeutic agent into the cells and selectively kill cancer cells. As a result, MCTs will be mediators of chemotherapeutic response, and their expression can be used as a molecular marker to predict response to chemotherapy.
Insights
Monocarboxylate transporters (MCTs) are key in cancer metabolism and pH regulation. Their elevated expression in tumors can be exploited to deliver chemotherapy, selectively killing cancer cells.
Area of Science:
- Cellular Biology
- Biochemistry
- Oncology
Background:
- Monocarboxylate transporters (MCTs), encoded by the SLC16 gene family, facilitate transmembrane transport of lactic acid and other monocarboxylic acids.
- Cancer cells exhibit altered metabolism with high glucose consumption and lactate production, upregulating MCTs for survival.
- MCT1 and MCT4 are crucial for lactate efflux and maintaining intracellular pH in tumor cells.
Purpose of the Study:
- To investigate the role of MCTs in cancer metabolism and their potential as therapeutic targets.
- To explore the involvement of MCTs in the uptake of chemotherapeutic agents.
- To evaluate MCT expression as a predictive marker for chemotherapy response.
Main Methods:
- Biochemical characterization of MCT family members.
- Analysis of MCT expression in cancer cells.
- Investigation of MCTs' role in lactate transport and pH regulation.
- Studies on MCT-mediated uptake of chemotherapeutic agents like 3-bromopyruvate.
Main Results:
- MCTs, particularly MCT1 and MCT4, are upregulated in cancer cells to support their metabolic phenotype.
- MCTs facilitate both lactate efflux and proton co-transport, aiding tumor survival.
- Elevated MCT expression enables the selective uptake of chemotherapeutics like 3-bromopyruvate into cancer cells.
- MCTs act as 'Trojan horses,' mediating the entry of drugs to selectively kill cancer cells.
Conclusions:
- MCTs are critical regulators of cancer cell metabolism and pH.
- MCTs represent attractive therapeutic targets for cancers with specific metabolic profiles.
- MCT expression levels can serve as a predictive biomarker for chemotherapy response, particularly with agents like 3-bromopyruvate.
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