Deciphering of the reactive oxygen species (ROS) induced calpain activation in cancer progression and its therapeutic potential

• Reactive oxygen species (ROS) induced calpain activation in cancer. • Reactive oxygen species induced calpain activation mechanism in cancer stem cells. • Crosstalk between different genes and calpain signalling pathways in cancer progression. • ROS-induced mitochondrial calpain activity influences retrograde nuclear gene expression, promoting the growth of cancer stem cells. • Targeting ROS-induced calpain activation approaches innovative cancer treatments and therapeutic interventions. Mitochondrial signalling plays a fundamental role in orchestrating essential intracellular functions, including cellular respiration, proliferation, nucleic acid synthesis, and oxidative stress management. The activation of calpain, a group of Ca 2+ -dependent cysteine proteases, by ROS-induced oxidative stress is linked to cancer progression. Calpain can be activated by ROS either through intracellular Ca 2+ elevation or via oxidative modifications of the protease, altering protein susceptibility to calpain cleavage. In tumour cell biology, ROS-activated calpains influence cell survival, migration, proliferation, apoptosis, and invasiveness. Several studies report unusual calpain expression in cancer cells. Various anticancer drugs induce cytotoxicity by activating calpain, significantly impacting cancer treatment strategies. This unique review explores the perspective of ROS-induced calpain activation and its pivotal role in cancer progression and therapeutics.