Ferroptosis open a new door for colorectal cancer treatment

Abstract

Colorectal cancer (CRC) is the third highest incidence and the second highest mortality malignant tumor in the world. The etiology and pathogenesis of CRC are complex. Due to the long course of the disease and no obvious early symptoms, most patients are diagnosed as middle and late stages. CRC is prone to metastasis, most commonly liver metastasis, which is one of the leading causes of death in CRC patients. Ferroptosis is a newly discovered cell death form with iron dependence, which is driven by excessive lipid peroxides on the cell membrane. It is different from other form of programmed cell death in morphology and mechanism, such as apoptosis, pyroptosis and necroptosis. Numerous studies have shown that ferroptosis may play an important role in the development of CRC. For advanced or metastatic CRC, ferroptosis promises to open a new door in the setting of poor response to chemotherapy and targeted therapy. This mini review focuses on the pathogenesis of CRC, the mechanism of ferroptosis and the research status of ferroptosis in CRC treatment. The potential association between ferroptosis and CRC and some challenges are discussed.

Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer

“…This suggests that the induction of iron-mediated cell death could serve as a therapeutic approach for CRC, particularly against drug-resistant CRC that is resistant to conventional medical interventions. 155,156 Several small molecule compounds derived from plants have demonstrated their ability to induce ferroptosis in CRC. Ginsenosides Rh4 and auriculasin were capable of inducing the accumulation of ROS and the onset of ferroptosis.…”

“…CRC cells, especially those with drug-resistant properties, exhibit elevated levels of iron and ROS. This suggests that the induction of iron-mediated cell death could serve as a therapeutic approach for CRC, particularly against drug-resistant CRC that is resistant to conventional medical interventions. , Several small molecule compounds derived from plants have demonstrated their ability to induce ferroptosis in CRC. Ginsenosides Rh4 and auriculasin were capable of inducing the accumulation of ROS and the onset of ferroptosis. , Treatment of CRC with punicic acid increased intracellular LPO, and when combined with docosahexaenoic acid, the cytotoxicity of punicic acid was synergistically enhanced .…”

Exploring the landscape of drug resistance in gastrointestinal cancer immunotherapy: A review

“…Another burgeoning area of research is the potential influence of the gut microbiome in shaping the resistance to immunotherapy. [ 59 ] Recent research has illuminated the possibility that specific microbiota residing in the gut may have the capacity to shape immune responses, thereby influencing the effectiveness of immunotherapy. Understanding the complex interactions between the gut microbiome and the immune system could potentially unlock novel strategies for microbiome modulation, thereby enhancing the efficacy of immunotherapy.…”

Total Synthesis and Stereochemical Assignment of Talaroconvolutin A and Talarofuranone: Gram‐scale Synthesis of Ferroptosis Inducer Talaroconvolutin A

“…Ferroptosis, which inhibits tumor proliferation and induces ferroptosis, has demonstrated efficacy in reversing drug resistance. [ 3 ] Recently, we found that talaroconvolutin A, which was first discovered by Kawai and coworkers from Talaromyces convolutus as an antifungal, [ 4 ] could kill colon cancer cells by inducing ferroptosis (HCT116, IC 50 1.22 μM; SW480, IC 50 1.40 μM; SW620, IC 50 1.27 μM). [ 5 ] The potency of talaroconvolutin A in inhibiting colon cancer cells via ferroptosis is considerably higher than that of erastin (a well‐known ferroptosis inducer), making it a novel candidate for CRC therapy resistance.…”