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Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy.
Radiol Oncol. 2019 03 28; 53(2):148-158.RO

Abstract

Background Platinum-based anticancer drugs are widely used in the chemotherapy of human neoplasms. The major obstacle for the clinical use of this class of drugs is the development of resistance and toxicity. It is therefore very important to understand the chemical properties, transport and metabolic pathways and mechanism of actions of these compounds. There is a large body of evidence that therapeutic and toxic effects of platinum drugs on cells are not only a consequence of covalent adducts formation between platinum complexes and DNA but also with RNA and many proteins. These processes determine molecular mechanisms that underlie resistance to platinum drugs as well as their toxicity. Increased expression levels of various transporters and increased repair of platinum-DNA adducts are both considered as the most significant processes in the development of drug resistance. Functional genomics has an increasing role in predicting patients' responses to platinum drugs. Genetic polymorphisms affecting these processes may play an important role and constitute the basis for individualized approach to cancer therapy. Similar processes may also influence therapeutic potential of nonplatinum metal compounds with anticancer activity. Conclusions Cisplatin is the most frequently used platinum based chemotherapeutic agent that is clinically proven to combat different types of cancers and sarcomas.

Authors+Show Affiliations

Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30956230

Citation

Makovec, Tomaz. "Cisplatin and Beyond: Molecular Mechanisms of Action and Drug Resistance Development in Cancer Chemotherapy." Radiology and Oncology, vol. 53, no. 2, 2019, pp. 148-158.
Makovec T. Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol. 2019;53(2):148-158.
Makovec, T. (2019). Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiology and Oncology, 53(2), 148-158. https://doi.org/10.2478/raon-2019-0018
Makovec T. Cisplatin and Beyond: Molecular Mechanisms of Action and Drug Resistance Development in Cancer Chemotherapy. Radiol Oncol. 2019 03 28;53(2):148-158. PubMed PMID: 30956230.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. A1 - Makovec,Tomaz, Y1 - 2019/03/28/ PY - 2018/07/20/received PY - 2018/09/05/accepted PY - 2019/4/9/pubmed PY - 2020/3/24/medline PY - 2019/4/9/entrez KW - chemotherapy KW - cisplatin KW - molecular mechanisms KW - resistance SP - 148 EP - 158 JF - Radiology and oncology JO - Radiol Oncol VL - 53 IS - 2 N2 - Background Platinum-based anticancer drugs are widely used in the chemotherapy of human neoplasms. The major obstacle for the clinical use of this class of drugs is the development of resistance and toxicity. It is therefore very important to understand the chemical properties, transport and metabolic pathways and mechanism of actions of these compounds. There is a large body of evidence that therapeutic and toxic effects of platinum drugs on cells are not only a consequence of covalent adducts formation between platinum complexes and DNA but also with RNA and many proteins. These processes determine molecular mechanisms that underlie resistance to platinum drugs as well as their toxicity. Increased expression levels of various transporters and increased repair of platinum-DNA adducts are both considered as the most significant processes in the development of drug resistance. Functional genomics has an increasing role in predicting patients' responses to platinum drugs. Genetic polymorphisms affecting these processes may play an important role and constitute the basis for individualized approach to cancer therapy. Similar processes may also influence therapeutic potential of nonplatinum metal compounds with anticancer activity. Conclusions Cisplatin is the most frequently used platinum based chemotherapeutic agent that is clinically proven to combat different types of cancers and sarcomas. SN - 1581-3207 UR - https://www.unboundmedicine.com/medline/citation/30956230/Cisplatin_and_beyond:_molecular_mechanisms_of_action_and_drug_resistance_development_in_cancer_chemotherapy_ L2 - https://www.degruyter.com/doi/10.2478/raon-2019-0018 DB - PRIME DP - Unbound Medicine ER -