ASCT2 and LAT1 Contribution to the Hallmarks of Cancer: From a Molecular Perspective to Clinical Translation

Autores da FMUP

• Carla Maria De Moura Lopes

  Autor

• Ana Margarida Barbosa Ribeiro Pereira

  Autor

• Rui Manuel De Medeiros Melo Silva

  Autor

Unidades de investigação

• Ciências da Saúde Pública e Forenses, e Educação Médica

• Medicina da Comunidade, Informação e Decisão em Saúde

Abstract

Simple Summary ASCT2 and LAT1 are amino acid transporters whose impact in cancer has been explored throughout the years. They have been associated with most currently accepted hallmarks of cancer, thus the aim of this review is to report the impact of these transporters in this disease, as well as their clinical significance and applications. ASCT2 and LAT1 have been identified as prognostic factors and potentially as therapeutic targets. In conclusion, the study and development of new inhibitors for these amino acid transporters constitutes a promising approach towards the improvement of cancer treatment and prognosis. 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.