Core Viewpoint - Ferroptosis has emerged as a promising anti-tumor treatment strategy, distinct from apoptosis and necroptosis, characterized by uncontrolled lipid peroxidation and high levels of ferrous ions (Fe2+) and reactive oxygen species (ROS) [2][3][7]. Group 1: Mechanism and Inducers of Ferroptosis - GPX4 utilizes glutathione (GSH) to reduce lipid peroxides to lipid alcohols, making targeting GPX4 or GSH a potential strategy for cancer therapy [3]. - Lipid peroxidation may serve as a "find me" signal, enhancing tumor immunotherapy effectiveness [3]. - Inducers of ferroptosis, such as RSL3 and erastin, have shown efficacy in inducing ferroptosis in mouse tumor models and human tumor cell lines [3][4]. Group 2: Research Findings on Acevaltrate - A recent study identified acevaltrate (ACE) as a novel ferroptosis inducer that targets both PCBP1/2 and GPX4 in colorectal cancer cells, leading to rapid and strong induction of ferroptosis [4][8]. - ACE increases intracellular Fe2+ levels by targeting and reducing the expression of iron chaperone proteins PCBP1/2, while also inhibiting GPX4 activity, disrupting the antioxidant system in colorectal cancer cells [9][12]. - Animal experiments indicate that ACE demonstrates superior therapeutic effects compared to known ferroptosis inducers and first-line clinical cancer drugs like capecitabine and TAS-102 [10][12]. Group 3: Implications for Clinical Treatment - The dual mechanism of ACE not only enhances the induction of ferroptosis but also addresses the compensatory resistance issues associated with single-target ferroptosis inducers [12]. - ACE's multi-target characteristics suggest a potential for high efficacy and low toxicity in selectively killing tumor cells, providing a new strategy for clinical treatment of colorectal cancer [12].