Gaseous signaling molecules and their application in resistant cancer treatment: from invisible to visible.

Abstract

Multidrug resistance (MDR) in cancer remains a critical obstacle for efficient chemotherapy. Many MDR reversal agents have been discovered but failed in clinical trials due to severe toxic effects. Gaseous signaling molecules (GSMs), such as oxygen, nitric oxide, hydrogen sulfide and carbon monoxide, play key roles in regulating cell biological function and MDR. Compared with other toxic chemosensitizing agents, GSMs are endogenous and biocompatible molecules with little side effects. Research show that GSM modulators, including pharmaceutical formulations of GSMs (combined with conventional chemotherapeutic drugs) and GSM-donors (small molecules with GSMs releasing property), can overcome or reverse MDR. This review discusses the roles of these four GSMs in modulating MDR, and summarizes GSMs modulators in treating cancers with drug resistance.