New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment
Although cisplatin has been a pivotal chemotherapy drug in treating patients with various types of cancer for decades, drug resistance has been a major clinical impediment. In general, cisplatin exerts cytotoxic effects in tumor cells mainly through the generation of DNA-platinum adducts and subsequ...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-08-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/20/17/4136 |
id |
doaj-17c3daf7138a43cf83fb6fc7e04bd99c |
---|---|
record_format |
Article |
spelling |
doaj-17c3daf7138a43cf83fb6fc7e04bd99c2020-11-25T02:01:47ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-08-012017413610.3390/ijms20174136ijms20174136New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to MicroenvironmentShang-Hung Chen0Jang-Yang Chang1National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanAlthough cisplatin has been a pivotal chemotherapy drug in treating patients with various types of cancer for decades, drug resistance has been a major clinical impediment. In general, cisplatin exerts cytotoxic effects in tumor cells mainly through the generation of DNA-platinum adducts and subsequent DNA damage response. Accordingly, considerable effort has been devoted to clarify the resistance mechanisms inside tumor cells, such as decreased drug accumulation, enhanced detoxification activity, promotion of DNA repair capacity, and inactivated cell death signaling. However, recent advances in high-throughput techniques, cell culture platforms, animal models, and analytic methods have also demonstrated that the tumor microenvironment plays a key role in the development of cisplatin resistance. Recent clinical successes in combination treatments with cisplatin and novel agents targeting components in the tumor microenvironment, such as angiogenesis and immune cells, have also supported the therapeutic value of these components in cisplatin resistance. In this review, we summarize resistance mechanisms with respect to a single tumor cell and crucial components in the tumor microenvironment, particularly focusing on favorable results from clinical studies. By compiling emerging evidence from preclinical and clinical studies, this review may provide insights into the development of a novel approach to overcome cisplatin resistance.https://www.mdpi.com/1422-0067/20/17/4136cisplatintumor microenvironmentdrug resistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shang-Hung Chen Jang-Yang Chang |
spellingShingle |
Shang-Hung Chen Jang-Yang Chang New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment International Journal of Molecular Sciences cisplatin tumor microenvironment drug resistance |
author_facet |
Shang-Hung Chen Jang-Yang Chang |
author_sort |
Shang-Hung Chen |
title |
New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment |
title_short |
New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment |
title_full |
New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment |
title_fullStr |
New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment |
title_full_unstemmed |
New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment |
title_sort |
new insights into mechanisms of cisplatin resistance: from tumor cell to microenvironment |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-08-01 |
description |
Although cisplatin has been a pivotal chemotherapy drug in treating patients with various types of cancer for decades, drug resistance has been a major clinical impediment. In general, cisplatin exerts cytotoxic effects in tumor cells mainly through the generation of DNA-platinum adducts and subsequent DNA damage response. Accordingly, considerable effort has been devoted to clarify the resistance mechanisms inside tumor cells, such as decreased drug accumulation, enhanced detoxification activity, promotion of DNA repair capacity, and inactivated cell death signaling. However, recent advances in high-throughput techniques, cell culture platforms, animal models, and analytic methods have also demonstrated that the tumor microenvironment plays a key role in the development of cisplatin resistance. Recent clinical successes in combination treatments with cisplatin and novel agents targeting components in the tumor microenvironment, such as angiogenesis and immune cells, have also supported the therapeutic value of these components in cisplatin resistance. In this review, we summarize resistance mechanisms with respect to a single tumor cell and crucial components in the tumor microenvironment, particularly focusing on favorable results from clinical studies. By compiling emerging evidence from preclinical and clinical studies, this review may provide insights into the development of a novel approach to overcome cisplatin resistance. |
topic |
cisplatin tumor microenvironment drug resistance |
url |
https://www.mdpi.com/1422-0067/20/17/4136 |
work_keys_str_mv |
AT shanghungchen newinsightsintomechanismsofcisplatinresistancefromtumorcelltomicroenvironment AT jangyangchang newinsightsintomechanismsofcisplatinresistancefromtumorcelltomicroenvironment |
_version_ |
1724955865343066112 |