Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity.

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Cisplatin is a vital platinum-based chemotherapy for solid tumors.
• Cisplatin-induced toxicities (CITs), including nephrotoxicity (CIN), peripheral neuropathy (CIPN), and ototoxicity (CIO), limit its clinical use.
• While cisplatin's anti-cancer mechanisms are known, the drivers of its toxicities are emerging.

Purpose of the Study:

• To review the common and distinct inflammatory hallmarks across different CITs.
• To elucidate the role of innate immune components in CIT development.
• To discuss current therapeutic strategies targeting pro-inflammatory pathways for mitigating CITs.

Main Methods:

• Literature review focusing on inflammation and innate immunity in cisplatin-induced toxicities.
• Analysis of studies investigating pro-inflammatory signaling pathways in CIN, CIPN, and CIO.
• Examination of current treatment approaches targeting inflammation.

Main Results:

• Inflammation, particularly from the innate immune system, is identified as a key instigator of CITs.
• Pro-inflammatory signaling is consistently induced in CIN, CIPN, and CIO.
• Distinct and common inflammatory markers are present across various CITs.

Conclusions:

• Inflammation plays a central role in the pathogenesis of cisplatin-induced toxicities.
• Targeting inflammatory pathways offers a promising strategy to reduce CITs.
• Mitigating CITs can help preserve cisplatin's efficacy and improve long-term patient health.