Abstract
Platinum drugs have been widely used for the treatment of several solid tumors. Although DNA has been recognized as the primary cellular target for these agents, there are unresolved issues concerning their effects and the molecular mechanisms underlying the antitumor efficacy. These cytotoxic agents interact with sub-cellular compartments other than the nucleus. Here, we review how such emerging phenomena contribute to the pharmacologic activity as well as to drug resistance phenotypes. DNA-unrelated effects of platinum drugs involve alterations at the plasma membrane and in endo-lysosomal compartments. A direct interaction with the mitochondria also appears to be implicated in drug-induced cell death. Moreover, the pioneering work of a few groups has shown that platinum drugs can act on the tumor microenvironment as well, and potentiate antitumor activity of the immune system. These poorly understood aspects of platinum drug activity sites may be harnessed to enhance their antitumor efficacy. A complete understanding of DNA-unrelated effects of platinum compounds might reveal new aspects of drug resistance allowing the implementation of the antitumor therapeutic efficacy of platinum compound-based regimens and minimization of their toxic side effects.
| Original language | English |
|---|---|
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Drug Resistance Updates |
| Volume | 20 |
| DOIs | |
| Publication status | Published - Jun 11 2015 |
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Keywords
- Cell death
- Drug resistance
- Lysosomes
- Mitochondria
- Platinum compounds
ASJC Scopus subject areas
- Cancer Research
- Infectious Diseases
- Oncology
- Pharmacology (medical)
- Pharmacology
Cite this
New mechanisms for old drugs : Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants. / Gatti, Laura; Cassinelli, Giuliana; Zaffaroni, Nadia; Lanzi, Cinzia; Perego, Paola.
In: Drug Resistance Updates, Vol. 20, 11.06.2015, p. 1-11.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - New mechanisms for old drugs
T2 - Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants
AU - Gatti, Laura
AU - Cassinelli, Giuliana
AU - Zaffaroni, Nadia
AU - Lanzi, Cinzia
AU - Perego, Paola
PY - 2015/6/11
Y1 - 2015/6/11
N2 - Platinum drugs have been widely used for the treatment of several solid tumors. Although DNA has been recognized as the primary cellular target for these agents, there are unresolved issues concerning their effects and the molecular mechanisms underlying the antitumor efficacy. These cytotoxic agents interact with sub-cellular compartments other than the nucleus. Here, we review how such emerging phenomena contribute to the pharmacologic activity as well as to drug resistance phenotypes. DNA-unrelated effects of platinum drugs involve alterations at the plasma membrane and in endo-lysosomal compartments. A direct interaction with the mitochondria also appears to be implicated in drug-induced cell death. Moreover, the pioneering work of a few groups has shown that platinum drugs can act on the tumor microenvironment as well, and potentiate antitumor activity of the immune system. These poorly understood aspects of platinum drug activity sites may be harnessed to enhance their antitumor efficacy. A complete understanding of DNA-unrelated effects of platinum compounds might reveal new aspects of drug resistance allowing the implementation of the antitumor therapeutic efficacy of platinum compound-based regimens and minimization of their toxic side effects.
AB - Platinum drugs have been widely used for the treatment of several solid tumors. Although DNA has been recognized as the primary cellular target for these agents, there are unresolved issues concerning their effects and the molecular mechanisms underlying the antitumor efficacy. These cytotoxic agents interact with sub-cellular compartments other than the nucleus. Here, we review how such emerging phenomena contribute to the pharmacologic activity as well as to drug resistance phenotypes. DNA-unrelated effects of platinum drugs involve alterations at the plasma membrane and in endo-lysosomal compartments. A direct interaction with the mitochondria also appears to be implicated in drug-induced cell death. Moreover, the pioneering work of a few groups has shown that platinum drugs can act on the tumor microenvironment as well, and potentiate antitumor activity of the immune system. These poorly understood aspects of platinum drug activity sites may be harnessed to enhance their antitumor efficacy. A complete understanding of DNA-unrelated effects of platinum compounds might reveal new aspects of drug resistance allowing the implementation of the antitumor therapeutic efficacy of platinum compound-based regimens and minimization of their toxic side effects.
KW - Cell death
KW - Drug resistance
KW - Lysosomes
KW - Mitochondria
KW - Platinum compounds
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UR - http://www.scopus.com/inward/citedby.url?scp=84930759388&partnerID=8YFLogxK
U2 - 10.1016/j.drup.2015.04.001
DO - 10.1016/j.drup.2015.04.001
M3 - Article
C2 - 26003720
AN - SCOPUS:84930759388
VL - 20
SP - 1
EP - 11
JO - Drug Resistance Updates
JF - Drug Resistance Updates
SN - 1368-7646
ER -