In the realm of cancer biology, metabolic reprogramming is a hallmark of cancer cells, enabling them to sustain rapid proliferation, evade cell death, and adapt to hostile microenvironments. Central to this reprogramming are amino acid transporters (AATs) such as SLC6A14, SLC38A5, SLC7A11, SLC7A5, and SLC1A5. These transporters function as nutrient conduits and tumor promoters, facilitating the uptake of essential amino acids that fuel biosynthetic pathways, activate the mTORC1 signaling pathway, and modulate stress responses crucial for tumor survival and progression. Despite significant progress, understanding the full spectrum of functions these AATs perform and their potential as drug targets remains an area of active investigation with many open questions.

This Research Topic aims to spotlight the multifaceted roles of amino acid transporters in cancer biology, emphasizing their involvement in mammalian target of rapamycin (mTORC1) signaling and nutrient scavenging mechanisms, such as autophagy and macropinocytosis, as well as ferroptosis. The goal is to explore the impact of AAT loss on critical metabolic pathways, including glycolysis, the TCA cycle, and oxidative phosphorylation. A particular focus will be given to regulatory interactions influenced by oncogenic mutations, such as p53 and Kras, and their effects on transporter expression and activity. The exploration of therapeutic potential through repurposed agents like niclosamide and carbidopa, along with addressing challenges such as systemic amino acid depletion, off-target effects, and compensatory mechanisms, will also be prioritized in the discussion.

To gather further insights into this Research Topic, we welcome articles addressing, but not limited to, the following themes:

- Mechanistic insights into AAT regulation and their role in cancer pathways

- The interplay between AATs and autophagy, macropinocytosis, and ferroptosis

- Impact of oncogenic mutations on AAT regulation and tumor metabolism

- Exploration of repurposed drugs and their efficacy in targeting AATs

- Overcoming challenges such as amino acid depletion and transporter compensatory mechanisms

We invite original research, reviews, and perspectives across these areas that collectively aim to increase our understanding of AATs as pivotal components in cancer metabolism. By integrating molecular insights with preclinical and clinical data, this Research Topic strives to highlight innovative strategies for targeting the metabolic dependencies that define tumor vulnerabilities, catalyzing future advancements in cancer therapy.

Dr Areti-Maria Vasilogianni is currently an employee at AstraZeneca, DMPK, Oncology R&D.

Are you interested in contributing a manuscript to this Research Topic?

Amino Acid Transporters in Cancer: Metabolic Regulators and Therapeutic Targets