New insights into mechanisms of cisplatin resistance: From tumor cell to microenvironment

Shang Hung Chen, Jang Yang Chang

Research output: Contribution to journalReview articlepeer-review

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number4136
JournalInternational journal of molecular sciences
Volume20
Issue number17
DOIs
Publication statusPublished - 2019 Sep 1

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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