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.
Highlights
Cisplatin (CDDP), a platinum-based anticancer agent, is one of the most commonly used chemotherapy drugs in the treatment of patients with various types of cancer, such as bladder, ovarian, head and neck, lung, testicular, cervical, esophageal, and breast cancer [1]
CDDP has demonstrated major clinical success in patients with various types of cancer for more than two decades; drug resistance of tumor cells has remained the main impediment for the clinical use of CDDP
Preclinical and clinical studies have showed that CDDP resistance is a complex biological phenomenon mediated by inner adaptive mechanisms of tumor cells responsive to CDDP stimulation and the interaction from any tumor microenvironment (TME) component
Summary
Cisplatin (CDDP), a platinum-based anticancer agent, is one of the most commonly used chemotherapy drugs in the treatment of patients with various types of cancer, such as bladder, ovarian, head and neck, lung, testicular, cervical, esophageal, and breast cancer [1]. The molecular structure of CDDP contains the basic platinum complex, two amides, and two chloride ligands in a cis elemental orientation This first metal-based chemotherapy drug was discovered by the Italian chemist Michele Peyrone in 1845, and its ability to inhibit cell division was recognized by the American biophysicist Dr Barnett Rosenberg in 1965. CDDP treatment has exhibited a high degree of activity against tumor growth in various solid cancers, and millions of patients have received this chemotherapy drug in their anticancer therapies. We present brief and to-the-point summaries concerning CDDP resistance in tumor cells and the TME These discussions focus on experimental evidence with clinical implications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
