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Journal of Molecular and Clinical Medicine   2018, Vol. 1 Issue (4): 205-212    DOI: 10.31083/j.jmcm.2018.04.403
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Novel aspects of the preclinical pharmacology of platinum compounds
Cristina Corno1, Paola Perego1, *()
1 Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133, Milan, Italy
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Platinum compounds are widely used antitumor agents known to interfere with DNA function by forming DNA crosslinks and DNA-protein crosslinks. Because of their electrophilicity, platinum compounds can interact with nucleophilic residues of all macromolecules. Consequently, this cross-linking inhibits DNA replication in cancer cells. Immunogenic and immunomodulating effects have been ascribed to platinum drugs, with differences and similarities among cisplatin, carboplatin and oxaliplatin. On the one hand, cisplatin is generally unable to induce immunogenic cell death; on the other hand, oxaliplatin appears to be a good inducer, thanks to its capability to efficiently trigger calreticulin exposure to the tumor cell plasma membrane. Conversely, cisplatin, carboplatin and oxaliplatin can relieve immunosuppressive networks e.g., by decreasing PDL-1 and PDL-2 in dendritic and tumor cells. Such drugs are also capable of modulating MHC molecules via IFN-β production and T-cell mediated lysis. The concentrations appear to be key in determining the immunomodulatory properties of these cytotoxic agents, with low in vivo doses usually playing stimulatory effects. As predicted from preclinical models, supportive results have emerged from clinical studies, particularly those based on chemotherapeutic regimens of platinum compounds combined with immunotherapeutics. Future therapeutic interventions are expected to benefit from a better definition of the molecular effects of platinum compounds on the immune system.

Key words:  Cisplatin      Carboplatin      Oxaliplatin      Immunogenic cell death      Immunostimulation     
Revised:  12 November 2018      Accepted:  02 December 2018      Published:  20 December 2018     
*Corresponding Author(s):  Perego Paola     E-mail:

Cite this article: 

Cristina Corno,Paola Perego. Novel aspects of the preclinical pharmacology of platinum compounds. Journal of Molecular and Clinical Medicine , 2018, 1(4): 205-212.

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Fig. 1.  Structures of the most commonly used platinum compounds. The dates of approval for clinical use are indicated together with the mechanism of action and cell response.

Fig. 2.  Schematic representation of platinum drug-induced immunogenic cell death. Examples of modes to render cisplatin capable to trigger immunogenic cell death (ICD) are shown in the box. The key players of ICD are also shown. Abbreviations: ER = endoplasmic reticulum; Zn= zinc; Hsp70/90 = Heat shock protein 70/90; ATP = adenosine triphosphate; HGMB1 = high-mobility group box protein 1; DAMPs = damage-associated molecular patterns; DC = dendritic cell; IL-β 1 = interleukin 1-beta; IFN-γ = interferon gamma.

Fig. 3.  Immunomodulatory activity of platinum compounds. The main recently reported aspects of the immunomodulatory activity of platinum compounds are shown.

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