Roles and therapeutic targeting of SLC transporters in gastrointestinal malignancies.

The solute carrier (SLC) transporter family, serving as metabolic gatekeepers, transports a range of substrates (nutrients, metabolites, ions, drugs) and regulates key physiological processes (proliferation, migration, angiogenesis, chemoresistance, immunomodulation, energy metabolism). Gastrointestinal malignancies are a leading cause of cancer-related deaths globally, marked by high prevalence and aggressive growth. Metabolic reprogramming, as an emerging cancer hallmark, promotes uncontrolled tumour proliferation. It dynamically adjusts the distribution of nutrients and energy in the tumour microenvironment, thereby regulating specific cellular processes. SLC transporters are widely expressed in the gastrointestinal tract, and their dysfunction can significantly affect tumour growth. Understanding the complex crosstalk between SLCs, cancer cell metabolism, and the tumour microenvironment is crucial for developing novel therapies. This review summarises the roles of SLCs in various oncogenic behaviours of gastrointestinal tumors, explains how their expression patterns and genetic variations contribute to chemoresistance, and assesses the clinical value of targeting SLC family proteins for therapeutic purposes.