Targeting Amino Acid Signaling and Metabolism in Cancer
A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".
Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 12250
Special Issue Editors
Interests: GCN2; ER stress; nutritional stress; lung cancer; metabolic dysfunction
Interests: Tumour hypoxia; HIF-1α; Glutamine Metabolism; Unfolded Protein Response; PERK; ATF4; Cancer Epigenetics
Special Issue Information
Dear Colleagues,
Cancer cells are characterized by an increased uptake and utilization of amino acids (AAs) in order to generate energy and biomass for growth. The essential role of these nutrients in tumor progression has motivated the development of several strategies based on chemo- and molecular targeted therapies, AA-degrading enzymes or dietary intervention to exploit cancer’s AA dependence. However, recent metabolomics-based studies have now highlighted that tumors are deficient in several AA, including glutamine, compared to their normal counterparts and that AA concentrations fluctuate both spatially and temporally within the tumor microenvironment. Indeed, inadequate tumor perfusion and the overexpression of AA-degrading enzymes (e.g. indoleamine-2,3-dioxygenase 1) leads to a heterogenous supply of AAs, resulting in the dysregulation of metabolic pathway activity and a wide spectrum of cellular alterations in malignant, stromal and immune tumor cells. Adaptation to this nutrient-poor microenvironment is orchestrated by a complex molecular network controlled by sensors including mTOR and GCN2, whose activities are additionally dependent on i) the nature of the lacking amino acid, ii) the availability of other metabolites (notably glucose and oxygen) and iii) intrinsic cellular signals. Investigating this multifaceted relationship between the phenotypic modifications triggered by AA deprivation requires the development of relevant preclinical models to reproduce the altered tumor nutritional micromilieu, paired with techniques and instrumentation to analyze these processes.
This Special Issue aims to provide a valuable resource to the scientific community regarding i) the current state-of-the-art concerning the fundamental contribution of amino acid metabolism and related signaling pathways to tumorigenesis; ii) novel findings regarding innovation in technical approaches, preclinical models and therapeutic strategies based on AA manipulation; and iii) a framework for prioritizing unanswered questions and future challenges concerning AA metabolism in tumors.
Dr. Cedric Chaveroux
Dr. Dean C. Singleton
Guest Editors
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