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  1. Article ; Online: Is it still worth pursuing the repurposing of metformin as a cancer therapeutic?

    Lord, Simon R / Harris, Adrian L

    British journal of cancer

    2023  Volume 128, Issue 6, Page(s) 958–966

    Abstract: Over the past 15 years, there has been great interest in the potential to repurpose the diabetes drug, metformin, as a cancer treatment. However, despite considerable efforts being made to investigate its efficacy in a number of large randomised clinical ...

    Abstract Over the past 15 years, there has been great interest in the potential to repurpose the diabetes drug, metformin, as a cancer treatment. However, despite considerable efforts being made to investigate its efficacy in a number of large randomised clinical trials in different tumour types, results have been disappointing to date. This perspective article summarises how interest initially developed in the oncological potential of metformin and the diverse clinical programme of work to date including our contribution to establishing the intra-tumoral pharmacodynamic effects of metformin in the clinic. We also discuss the lessons that can be learnt from this experience and whether a further clinical investigation of metformin in cancer is warranted.
    MeSH term(s) Humans ; Metformin/therapeutic use ; Drug Repositioning ; Hypoglycemic Agents/therapeutic use ; Neoplasms/drug therapy
    Chemical Substances Metformin (9100L32L2N) ; Hypoglycemic Agents
    Language English
    Publishing date 2023-02-23
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-023-02204-2
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  2. Article ; Online: COVID-19 and cancer research.

    Harris, Adrian L

    British journal of cancer

    2020  Volume 123, Issue 5, Page(s) 689–690

    Abstract: The COVID-19 pandemic has had a devastating effect on human lives and society. The accompanying editorial summarises some of the major effects on cancer patients and impacts on cancer research. These may be mitigated by appropriate responses from ... ...

    Abstract The COVID-19 pandemic has had a devastating effect on human lives and society. The accompanying editorial summarises some of the major effects on cancer patients and impacts on cancer research. These may be mitigated by appropriate responses from governments, research funders, charities, universities, industry and the public. It is already clear that different approaches to management have drastically different outcomes.
    MeSH term(s) Betacoronavirus ; Biomedical Research/economics ; Biomedical Research/trends ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/virology ; Delivery of Health Care/trends ; Humans ; Neoplasms/drug therapy ; Neoplasms/immunology ; Pandemics/prevention & control ; Patient Isolation ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/virology ; Quarantine ; Risk Factors ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-06-26
    Publishing country England
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-020-0960-1
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  3. Article ; Online: Role of Hypoxia in the Interferon Response.

    Arnaiz, Esther / Harris, Adrian L

    Frontiers in immunology

    2022  Volume 13, Page(s) 821816

    Abstract: In solid tumors, as the tumor grows and the disease progresses, hypoxic regions are often generated, but in contrast to most normal cells which cannot survive under these conditions, tumour cells adapt to hypoxia by HIF-driven mechanisms. Hypoxia can ... ...

    Abstract In solid tumors, as the tumor grows and the disease progresses, hypoxic regions are often generated, but in contrast to most normal cells which cannot survive under these conditions, tumour cells adapt to hypoxia by HIF-driven mechanisms. Hypoxia can further promote cancer development by generating an immunosuppressive environment within the tumour mass, which allows tumour cells to escape the immune system recognition. This is achieved by recruiting immunosuppressive cells and by upregulating molecules which block immune cell activation. Hypoxia can also confer resistance to antitumor therapies by inducing the expression of membrane proteins that increase drug efflux or by inhibiting the apoptosis of treated cells. In addition, tumor cells require an active interferon (IFN) signalling pathway for the success of many anticancer therapies, such as radiotherapy or chemotherapy. Therefore, hypoxic effects on this pathway needs to be addressed for a successful treatment.
    MeSH term(s) Apoptosis ; Humans ; Hypoxia/metabolism ; Interferons/pharmacology ; Neoplasms ; Signal Transduction
    Chemical Substances Interferons (9008-11-1)
    Language English
    Publishing date 2022-02-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.821816
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  4. Article ; Online: Development of cancer metabolism as a therapeutic target: new pathways, patient studies, stratification and combination therapy.

    Harris, Adrian L

    British journal of cancer

    2019  Volume 122, Issue 1, Page(s) 1–3

    Abstract: Cancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and ... ...

    Abstract Cancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and clinical studies. What emerges are the large differences between tissues, tumour types and intratumour heterogeneity. However, synergies with inhibition of metabolic pathways have been found for many drugs and therapeutic approaches, and a critical role of window studies and translational trial design is key to success.
    MeSH term(s) Animals ; Azetidines/pharmacology ; Azetidines/therapeutic use ; Biomarkers, Tumor ; Clinical Trials as Topic ; Drug Therapy, Combination ; Fatty Acid Synthase, Type I/antagonists & inhibitors ; Fatty Acids/metabolism ; Glycolysis/drug effects ; Humans ; Mice ; Molecular Targeted Therapy/methods ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Nitriles/pharmacology ; Nitriles/therapeutic use ; Pyrazoles/pharmacology ; Pyrazoles/therapeutic use ; Signal Transduction/drug effects
    Chemical Substances 4-(1-(5-(3,4-dimethyl-1H-pyrazol-5-yl)-2,4-dimethylbenzoyl)azetidin-3-yl)benzonitrile ; Azetidines ; Biomarkers, Tumor ; Fatty Acids ; Nitriles ; Pyrazoles ; FASN protein, human (EC 2.3.1.85) ; Fatty Acid Synthase, Type I (EC 2.3.1.85)
    Language English
    Publishing date 2019-12-10
    Publishing country England
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-019-0666-4
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  5. Article: COVID-19 and cancer research

    Harris, Adrian L

    Br. j. cancer

    Abstract: The COVID-19 pandemic has had a devastating effect on human lives and society. The accompanying editorial summarises some of the major effects on cancer patients and impacts on cancer research. These may be mitigated by appropriate responses from ... ...

    Abstract The COVID-19 pandemic has had a devastating effect on human lives and society. The accompanying editorial summarises some of the major effects on cancer patients and impacts on cancer research. These may be mitigated by appropriate responses from governments, research funders, charities, universities, industry and the public. It is already clear that different approaches to management have drastically different outcomes.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32591747
    Database COVID19

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  6. Article ; Online: COVID-19 and cancer research

    Harris, Adrian L.

    British Journal of Cancer

    2020  Volume 123, Issue 5, Page(s) 689–690

    Keywords Cancer Research ; Oncology ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-020-0960-1
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  7. Article: Matters Arising: PREDICT underestimates survival of patients with HER2-positive early-stage breast cancer.

    Alaa, Ahmed M / Harris, Adrian L / van der Schaar, Mihaela

    NPJ breast cancer

    2023  Volume 9, Issue 1, Page(s) 13

    Language English
    Publishing date 2023-03-16
    Publishing country United States
    Document type Letter
    ISSN 2374-4677
    ISSN 2374-4677
    DOI 10.1038/s41523-023-00514-5
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  8. Article ; Online: Targeting mitochondrial oxidative phosphorylation: lessons, advantages, and opportunities.

    Machado, Nicole D / Heather, Lisa C / Harris, Adrian L / Higgins, Geoff S

    British journal of cancer

    2023  Volume 129, Issue 6, Page(s) 897–899

    MeSH term(s) Humans ; Oxidative Phosphorylation ; Mitochondria/metabolism ; Phosphorylation
    Language English
    Publishing date 2023-08-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-023-02394-9
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  9. Article ; Online: A New Hydroxy Metabolite of 2-Oxoglutarate Regulates Metabolism in Hypoxia.

    Harris, Adrian L

    Cell metabolism

    2015  Volume 22, Issue 2, Page(s) 198–200

    Abstract: Two articles in this issue (Intlekofer et al., 2015; Oldham et al., 2015) show a new metabolic pathway regulated by hypoxia, but independently of HIF1 or HIF2. L-2-hydroxyglutarate, produced in hypoxia by malate dehydrogenases and LDHA, is a potent ... ...

    Abstract Two articles in this issue (Intlekofer et al., 2015; Oldham et al., 2015) show a new metabolic pathway regulated by hypoxia, but independently of HIF1 or HIF2. L-2-hydroxyglutarate, produced in hypoxia by malate dehydrogenases and LDHA, is a potent inhibitor of KDM4C, and through redox stress reduces glycolysis.
    Language English
    Publishing date 2015-08-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2176834-1
    ISSN 1932-7420 ; 1550-4131
    ISSN (online) 1932-7420
    ISSN 1550-4131
    DOI 10.1016/j.cmet.2015.07.016
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  10. Article: The prognostic and therapeutic implications of distinct patterns of argininosuccinate synthase 1 (ASS1) and arginase-2 (ARG2) expression by cancer cells and tumor stroma in non-small-cell lung cancer.

    Giatromanolaki, Alexandra / Harris, Adrian L / Koukourakis, Michael I

    Cancer & metabolism

    2021  Volume 9, Issue 1, Page(s) 28

    Abstract: Background: Arginine (Arg) is essential for cancer cell growth and also for the activation of T cells. Thus, therapies aiming to reduce Arg utilization by cancer may prove detrimental for the immune response.: Methods: We examined the expression of ... ...

    Abstract Background: Arginine (Arg) is essential for cancer cell growth and also for the activation of T cells. Thus, therapies aiming to reduce Arg utilization by cancer may prove detrimental for the immune response.
    Methods: We examined the expression of two major enzymes involved in arginine depletion and replenishment, namely arginase ARG2 and argininosuccinate synthase ASS1, respectively, in a series of 98 NSCLCs. Their association with immune infiltrates and the postoperative outcome were also studied.
    Results: ARG2 was expressed mainly by cancer-associated fibroblasts (CAFs) (58/98 cases; 59.2%), while ASS1 by cancer cells (75/98 cases; 76.5%). ASS1 and ARG2 expression patterns were not related to hypoxia markers. Auxotrophy, implied by the lack of expression of ASS1 in cancer cells, was associated with high angiogenesis (p < 0.02). ASS1 expression by cancer cells was associated with a high density of iNOS-expressing tumor-infiltrating lymphocytes (
    Conclusions: ARG2 and ASS1 enzymes are extensively expressed in NSCLC stroma and cancer cells, respectively. Auxotrophic tumors have a poor prognosis, potentially by utilizing Arg, thus reducing Arg-dependent TIL anti-tumor activity. ASS1 expression in cancer cells would allow Arg fueling of
    Language English
    Publishing date 2021-08-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2700141-6
    ISSN 2049-3002
    ISSN 2049-3002
    DOI 10.1186/s40170-021-00264-7
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