For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
3
views
148
references
 Top references
cited by
15
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      350
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Amino Acid Metabolism in Cancer Drug Resistance

      Author(s): ,
      Publication date Created:
      Publication date (Electronic):
      Journal: Cells
      Publisher: MDPI AG

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Despite the numerous investigations on resistance mechanisms, drug resistance in cancer therapies still limits favorable outcomes in cancer patients. The complexities of the inherent characteristics of tumors, such as tumor heterogeneity and the complicated interaction within the tumor microenvironment, still hinder efforts to overcome drug resistance in cancer cells, requiring innovative approaches. In this review, we describe recent studies offering evidence for the essential roles of amino acid metabolism in driving drug resistance in cancer cells. Amino acids support cancer cells in counteracting therapies by maintaining redox homeostasis, sustaining biosynthetic processes, regulating epigenetic modification, and providing metabolic intermediates for energy generation. In addition, amino acid metabolism impacts anticancer immune responses, creating an immunosuppressive or immunoeffective microenvironment. A comprehensive understanding of amino acid metabolism as it relates to therapeutic resistance mechanisms will improve anticancer therapeutic strategies.

          Related collections

          Most cited references148

          • Record: found
          • Abstract: found
          • Article: not found

          CD8 + T cells regulate tumor ferroptosis during cancer immunotherapy

          Weimin Wang, Michael Green, Jae Eun Choi … (2019)
          Summary Cancer immunotherapy restores and/or enhances effector function of CD8+ T cells in the tumor microenvironment 1,2 . CD8+ T cells activated by cancer immunotherapy execute tumor clearance mainly by inducing cell death through perforin-granzyme- and Fas/Fas ligand-pathways 3,4 . Ferroptosis is a form of cell death that differs from apoptosis and results from iron-dependent lipid peroxide accumulation 5,6 . Although it was mechanistically illuminated in vitro 7,8 , emerging evidence has shown that ferroptosis may be implicated in a variety of pathological scenarios 9,10 . However, the involvement of ferroptosis in T cell immunity and cancer immunotherapy is unknown. Here, we find that immunotherapy-activated CD8+ T cells enhance ferroptosis-specific lipid peroxidation in tumor cells, and in turn, increased ferroptosis contributes to the anti-tumor efficacy of immunotherapy. Mechanistically, interferon gamma (IFNγ) released from CD8+ T cells downregulates expression of SLC3A2 and SLC7A11, two subunits of glutamate-cystine antiporter system xc-, restrains tumor cell cystine uptake, and as a consequence, promotes tumor cell lipid peroxidation and ferroptosis. In preclinical models, depletion of cyst(e)ine by cyst(e)inase in combination with checkpoint blockade synergistically enhances T cell-mediated anti-tumor immunity and induces tumor cell ferroptosis. Expression of system xc- is negatively associated with CD8+ T cell signature, IFNγ expression, and cancer patient outcome. Transcriptome analyses before and during nivolumab therapy reveal that clinical benefits correlate with reduced expression of SLC3A2 and increased IFNγ and CD8. Thus, T cell-promoted tumor ferroptosis is a novel anti-tumor mechanism. Targeting tumor ferroptosis pathway constitutes a therapeutic approach in combination with checkpoint blockade.
          Article 0 comments Cited 1032 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cancer drug resistance: an evolving paradigm.

            Caitriona Holohan, Sandra Van Schaeybroeck, Daniel Longley … (2013)
            Resistance to chemotherapy and molecularly targeted therapies is a major problem facing current cancer research. The mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to therapies that are designed to be selective for specific molecular targets share many features, such as alterations in the drug target, activation of prosurvival pathways and ineffective induction of cell death. With the increasing arsenal of anticancer agents, improving preclinical models and the advent of powerful high-throughput screening techniques, there are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.
            Article 0 comments Cited 762 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A view on drug resistance in cancer

              Neil Vasan, José Baselga, David Hyman (2019)
              The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling. These different approaches could eventually be synthesized for each tumour at any decision point and used to inform the choice of therapy.
              Article 0 comments Cited 680 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (publisher-id): CELLC6
                Title: Cells
                Abbreviated Title: Cells
                Publisher: MDPI AG
                ISSN (Electronic): 2073-4409
                Publication date Created: January 2022
                Publication date (Electronic): January 02 2022
                Volume: 11
                Issue: 1
                Page: 140
                Article
                DOI: 10.3390/cells11010140
                PubMed ID: 35011702
                SO-VID: 650b8d16-33e9-4a7e-add4-1c7481426ccd
                Copyright © © 2022
                License:

                https://creativecommons.org/licenses/by/4.0/

                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content350

                See all similar

                Cited by15

                See all cited by

                Most referenced authors3,178

                See all reference authors