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    Combination chemotherapy: a modern approach to target cancer with dual-action Tyrosine Kinase inhibitor-Platinum based drugs.


    Beirne, Darren (2024) Combination chemotherapy: a modern approach to target cancer with dual-action Tyrosine Kinase inhibitor-Platinum based drugs. PhD thesis, National University of Ireland Maynooth.

    [thumbnail of DFB Final Thesis Combined 10-02-2025.pdf] Text
    DFB Final Thesis Combined 10-02-2025.pdf
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    Abstract

    Platinum complexes as anticancer drugs (i.e. cisplatin, carboplatin, oxalilplatin) were discovered decades ago and have been approved and are worldwide used to treat a variety of tumours. Their activity is limited by dose-dependent side effects (nephro-, neuro- and ototoxicity) and the lack of selectivity toward cancer tissue with respect to healthy cells remains one of the major drawbacks. Combination chemotherapy is a burgeoning strategy that consists of combining in the same molecule two different drugs with two different mechanisms of action that can operate simultaneously, targeting different features on the cancer cell. Tyrosine kinases (TK) are promising targets in oncology and play a major role in cell regulation pathways (e.g. metabolism, transcription, cell division and programmed cell death) and TK deregulation is often related to cancer onset. Currently, the activity of platinum-based drugs against certain tumours, is limited because resistance is often acquired after few chemotherapeutic cycles. The aim of this project is to exploit the combination chemotherapy strategy to develop new drugs that will target cancer, combining in one unique molecule, the DNA damaging activity of platinum with TK inhibitors. Imatinib, Nilotinib and Sunitinib are known TKs inhibitors that are FDA approved to treat solid tumors, such as gastrointestinal stromal cancer and renal cell carcinoma. The two active components (platinum(II) and TK inhibitor) are released simultaneously upon intracellular reduction or hydrolysis, and work in cooperation to increase the overall anticancer efficacy.
    Item Type: Thesis (PhD)
    Keywords: Combination chemotherapy; modern approach; cancer; dual-action Tyrosine Kinase inhibitor-Platinum;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 19639
    Depositing User: IR eTheses
    Date Deposited: 03 Apr 2025 13:58
    Funders: Research Ireland
    URI: https://mural.maynoothuniversity.ie/id/eprint/19639
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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