The role of the amino acid transporters ASCT2 and LAT1 in cancer has been explored throughout the years. In this review, we report their impact on the hallmarks of cancer, as well as their clinical significance. Overall, both proteins have been associated with cell death resistance through dysregulation of caspases and sustainment of proliferative signaling through mTOR activation. Furthermore, ASCT2 appears to play an important role in cellular energetics regulation, whereas LAT1 expression is associated with angiogenesis and invasion and metastasis activation. The molecular impact of these proteins on the hallmarks of cancer translates into various clinical applications and both transporters have been identified as prognostic factors in many types of cancer. Concerning their role as therapeutic targets, efforts have been undertaken to synthesize competitive or irreversible ASCT2 and LAT1 inhibitors. However, JHP203, a selective inhibitor of the latter, is, to the best of our knowledge, the only compound included in a Phase 1 clinical trial. In conclusion, considering the usefulness of ASCT2 and LAT1 in a variety of cancer-related pathways and cancer therapy/diagnosis, the development and testing of novel inhibitors for these transporters that could be evaluated in clinical trials represents a promising approach to cancer prognosis improvement.

Gastric cancer (GC) screening is arguable in most Western countries. Liquid biopsies are a great promise to answer the unmet need for less invasive diagnostic biomarkers in GC. Thus, we aimed at systematically reviewing the current knowledge on liquid biopsy-based biomarkers in GC screening. A systematic search on PubMed/MEDLINE and Scopus databases was performed on published articles reporting the use of non-blood specimen (saliva, gastric juice [GJ], urine and stool) on GC diagnosis. 3208 records were retrieved by June 2022. After removal of duplicate records, 2379 abstracts were screened, and 84 full texts included in this systematic review. More than 90% of studies were reported on Asian populations.Overall, 9 studies explored stool-, 12 saliva-, and 29 urine-derived biomarkers for GC detection. Additionally, 37 studies, representing the majority, analyzed GJ, focusing on nucleic acid molecules. Several miRNAs and lncRNA molecules have been associated with GC risk, particularly miR-21 (area under the curve [AUC] = 0.97, 95% CI: 0.94-1.00). Considering salivary biomarkers, the best described model in validation sets included the soybean agglutinin and Vicia villosa agglutinin lectins (AUC = 0.89, 95% CI: 0.80-0.99). Most studies in urine carried out metabolomic approaches, with two discriminatory models presenting AUC values superior to 0.97. This systematic review emphasizes the potential role of non-blood-based biomarkers, although further validation, particularly in Western countries, is mandatory, namely for noninvasive screening and/or monitoring, as well as the use of GJ as a tool to enhance upper gastrointestinal endoscopy accuracy.