Work

Targeting Ferroptosis to Overcome Drug Resistance in Cancer: Molecular Mechanisms and Therapeutic Prospects

Year: 2025

Type: article

Abstract: Drug resistance in cancer cells remains a major obstacle limiting the clinical efficacy of current anticancer therapies. The induction of ferroptosis, an iron-dependent, regulated form of cell death, may offer an alternative therapeutic strategy to overcome such resistance. The generation of reactive oxygen species (ROS) has been implicated in this process, and depending on the cellular context, ROS can be either detrimental or beneficial. Ferroptosis can be effectively triggered in drug-resistant cancer cells in which ROS levels are often highly elevated. Key signaling pathways, including receptor tyrosine kinase (RTK), mitogen-activated protein kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (NRF2), are promising targets for modulating ROS homeostasis and sensitizing cancer cells to ferroptosis. In this review, we discuss the molecular mechanisms governing ferroptosis, the interplay between ROS and ferroptosis resistance, and emerging therapeutic approaches designed to enhance ferroptosis induction in drug-resistant cancer cells. Altogether, a combination of ferroptosis inducers and conventional treatments may improve the therapeutic efficacy and help overcome resistance mechanisms.

Source: Biomolecules & Therapeutics

DOI: 10.4062/biomolther.2025.211

Authors: Sang Hoon Joo, Yong-Yeon Cho, Jung-Hyun Shim

Institutions: Daegu Catholic University, Catholic University of Korea, Mokpo National University, China-US (Henan) Hormel Cancer Institute

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Catholic University of Daegu, Ministry of Education, National Research Foundation of Korea, Ministry of Science and ICT, South Korea