Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity

Cisplatin is a platinum-based chemotherapeutic that has long since been effective against a variety of solid-cancers, substantially improving the five-year survival rates for cancer patients. Its use has also historically been limited by its adverse drug reactions, or cisplatin-induced toxicities (C...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-06, Vol.23 (13), p.7227
Main Authors: Domingo, Ivan K, Latif, Asna, Bhavsar, Amit P
Format: Article
Language:English
Subjects:
Antigens
Antineoplastic Agents - adverse effects
Antitumor activity
Cancer
Cancer therapies
Cell cycle
Cell division
Chemokines
Chemotherapy
Cisplatin
Cisplatin - pharmacology
Cytokines
Cytotoxicity
Gene expression
Humans
Immune system
Inflammation
Inflammation - drug therapy
Innate immunity
Mitochondrial DNA
Neoplasms - chemically induced
Neoplasms - drug therapy
Ototoxicity
Oxidative stress
Pathogens
Patients
Peripheral Nervous System Diseases - chemically induced
Peripheral neuropathy
pro-inflammatory
Proteins
R&D
Research & development
Review
Signal Transduction
signalling
Toxicity
Transcription factors
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Summary:Cisplatin is a platinum-based chemotherapeutic that has long since been effective against a variety of solid-cancers, substantially improving the five-year survival rates for cancer patients. Its use has also historically been limited by its adverse drug reactions, or cisplatin-induced toxicities (CITs). Of these reactions, cisplatin-induced nephrotoxicity (CIN), cisplatin-induced peripheral neuropathy (CIPN), and cisplatin-induced ototoxicity (CIO) are the three most common of several CITs recognised thus far. While the anti-cancer activity of cisplatin is well understood, the mechanisms driving its toxicities have only begun to be defined. Most of the literature pertains to damage caused by oxidative stress that occurs downstream of cisplatin treatment, but recent evidence suggests that the instigator of CIT development is inflammation. Cisplatin has been shown to induce pro-inflammatory signalling in CIN, CIPN, and CIO, all of which are associated with persisting markers of inflammation, particularly from the innate immune system. This review covered the hallmarks of inflammation common and distinct between different CITs, the role of innate immune components in development of CITs, as well as current treatments targeting pro-inflammatory signalling pathways to conserve the use of cisplatin in chemotherapy and improve long-term health outcomes of cancer patients.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23137227