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1 2013

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Mechanizm oporności na leki platynowe oraz strategie pokonywania tego zjawiska

Weiss-Gradzińska W., Krzempek W., Trynda-Lemiesz L.

Wiadomości Chemiczne

2013

[Z] 67, 11-12

1105--1128

Platinum drugs belong to one of the oldest [2] and best investigated groups of cytotoxic drugs. On account of their high efficacy and alkylating-like action [14] they are used in a treatment of various types of neoplasms [3–5]. Despite investigators’ best efforts survival time of patients diagnosed with cancer is still short. Responsible for the fact is high toxicity of used therapeutic methods and development of resistance to them [3–5, 19]. In this paper authors review reasons behind decreased sensitivity of neoplastic cells to platinum treatment and discuss the newest promising trends in its overcoming. Due to different properties of neoplastic cells, availability of a chemotherapeutic agent inside a tumour is limited [9–12]. Moreover continuous development of resistance to platinum drugs further decreases their cellular concentration and inactivates their functions. Also owing to increased activity of DNA repair systems, higher tolerance to genome deformations and numerous mechanisms that lead to impaired apoptosis, drug efficacy is reduced [3-5, 19]. In order to increase a potency of platinum agents new therapeutic strategies are investigated. Coadministration with resistance modulators [20, 22, 23] and combination therapy with other antineoplastic drugs [8, 24–30] have already proved their effectiveness. Additionally, newer generations of platinum drugs are developed [15–18]. Mostly platinum(IV) prodrug complexes often releasing axial ligands with their own pharmacological action [5, 6, 31], but also multi-nuclear platinum compounds that form more complex DNA-adducts [32–35]. Other strategies include the development of innovative dosage forms such as single walled carbon nanotubes (SWCNTs), multiwalled carbon nanotubes (MWCNTs) [38, 39] or encapsulation [36, 37]. Finally utilisation of oncolytic viruses could be a way to selectively destroy neoplastically transformed cells [40].