Ferroptosis inducers: A new frontier in cancer therapy.

Bioorg Chem

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang 110016, China; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan; Program of Biology, Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates; Program of Bioengineering, Division of Engineering, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates; Department of Biomedical Engineering, Tandon School of Engineering, New York University, MetroTech, Brooklyn, NY 11201, United States. Electronic address:

Published: May 2024

AI Article Synopsis

  • * Traditional ferroptosis inducers like erastin and RSL3 show great promise for clinical use, leading to the development of new small molecule inducers that are more stable and specific, avoiding apoptosis while targeting cancer cells.
  • * Despite progress, challenges such as drug delivery, tumor targeting, and circulation time remain, prompting research into innovative delivery systems for more effective cancer treatments using ferroptosis inducers.

Article Abstract

Ferroptosis represents a non-apoptotic form of programmed cell death characterized by iron-dependent lipid peroxidation. This cell death modality not only facilitates the direct elimination of cancer cells, but also enhances their susceptibility to other pharmacological anti-cancer agents. The burgeoning interest in ferroptosis has been driven by a growing body of evidence that underscores the efficiency and minimal toxicity of ferroptosis inducers. Traditional inducers, such as erastin and RSL3 have shown substantial promise in clinical applications due to their potent therapeutic effects. Their significant potential of these inducers has spurred the development of a variety of small molecule ferroptosis inducers. These novel inducers boast an enhanced structural variety, improved metabolic stability, the capability to initiate ferroptosis without triggering apoptosis, making them well-suited for in vivo use. Despite these advancements, challenges still remain, particularly concerning the drug delivery, tumor specificity, and circulation duration of these small molecules in vivo. Addressing these challenges, contemporary research has pivoted towards innovative delivery systems tailored for ferroptosis inducers to facilitate precise, targeted, and synegestic therapeutic delivery. This review scrutinizes the latest progress in small molecule ferroptosis inducers and nano drug delivery systems geared towards ferroptosis sensitization. Furthermore, it delineated the prospective therapeutic advantages and the existing hurdles in the development of ferroptosis inducers for malignant tumor treatment.

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Source
http://dx.doi.org/10.1016/j.bioorg.2024.107331DOI Listing

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