SLC and ABC Transporters in Lung Cancer: Orchestrators of Malignancy and Therapeutic Resistance

BACKGROUND: Lung cancer remains a leading cause of global cancer mortality, with therapeutic efficacy significantly hampered by intrinsic and acquired therapy resistance. Solute carrier (SLC) and ATP-binding cassette (ABC) transporters have emerged as pivotal regulators orchestrating the transmembrane transport of diverse substrates to critically influence lung cancer progression and treatment response. SCOPE OF REVIEW: This review systematically examines the pathophysiological roles of key transporters in lung cancer progression and therapeutic response, with a particular emphasis on their functions in mediating crosstalk within the tumor microenvironment (TME). It assesses the current knowledge in this field, elucidates the underlying molecular mechanisms, and highlights potential avenues for future research and clinical translation. MAJOR CONCLUSIONS: SLC and ABC transporters critically contribute to the aggressiveness of lung cancer by orchestrating multiple facets of its malignant phenotype. This encompasses promoting cell proliferation, suppressing cell death, facilitating tumor invasion and metastasis, sustaining cancer stem cell (CSC) self-renewal, and modulating chemotherapy sensitivity and resistance. Furthermore, they mediate immunosuppression within the TME through dynamic crosstalk with resident stromal and immune cells. Thus, the substantial involvement of SLC and ABC transporters in lung cancer pathogenesis and therapeutic resistance definitively positions them as pivotal molecular vulnerabilities and actionable targets for developing novel therapeutic strategies to overcome drug resistance and improve clinical outcomes.