Ferroptosis as a Pharmacological Target in Therapy-Resistant Solid Tumors

Therapy resistance remains one of the most critical challenges in oncology, limiting the long-term efficacy of chemotherapy, targeted agents, and immunotherapy across solid tumor types. Ferroptosis has emerged as a mechanistically distinct vulnerability in cancer cells. Critically, therapy-resistant and dedifferentiated tumor cells frequently depend on the same glutathione and lipid-detoxification programs that ferroptosis disrupts, making this pathway a compelling pharmacological entry point. Epigenetic and non-coding RNA networks add an additional layer of regulation, modulating ferroptotic sensitivity in a tumor-type- and context-dependent manner.This Research Topic aims to deepen the understanding of ferroptosis as a druggable mechanism in solid tumors, with particular emphasis on the molecular and epigenetic networks that govern sensitivity and resistance to ferroptotic cell death. We seek studies that characterize the regulatory axes controlling ferroptosis, including ncRNA-mediated, epigenetic, and metabolic mechanisms, and that identify compounds or strategies capable of inducing ferroptosis with selectivity for malignant cells. We also welcome work exploring how ferroptosis intersects with the tumor microenvironment, tumor immunity, and metastatic programs. Contributions addressing the clinical translation of these findings, including biomarker identification, combination strategies with existing therapies, and the pharmacological basis for overcoming ferroptosis resistance, are particularly encouraged. Together, these contributions will help define a rigorous mechanistic and translational framework for exploiting ferroptosis in therapy-resistant solid tumors.We welcome Original Research, Reviews, Mini Reviews, and Brief Research Reports addressing, but not limited to:• Molecular and epigenetic regulation of ferroptosis (ncRNAs, m6A modification, chromatin remodeling) and its functional impact on anti-cancer efficacy• Druggable ferroptosis regulators (GPX4, system xc−, FSP1, ACSL4, iron metabolism) and their validation as therapeutic targets• Pharmacological modulation of ferroptotic sensitivity within the tumor microenvironment and tumor immunity• Ferroptosis-targeted strategies to limit metastasis and progression• Combination strategies linking ferroptosis induction with chemotherapy, targeted therapy, radiotherapy, or immunotherapyStudies should demonstrate selectivity toward cancer cells, validate findings across multiple cancer cell lines or in vivo models, and comprehensively elaborate the pharmacological effects and anti-tumor efficacy of candidate agents. Purely synthetic or computational work without experimental verification of anti-cancer activity falls outside the scope of this Research Topic. The collection also excludes work focused only on natural-product isolation, prognosis modeling, or therapy side effects.Topic Editor Leif Nietzel has a pending patent and three related patent disclosures concerning the use of a ferroptosis inducer in cancer. The other Topic Editors declare no competing interests with regard to this Research Topic. Topic editors: Leif Neitzel, Mateusz Kciuk, Zhe Wang Source: https://www.frontiersin.org/research-topics/85637/ferroptosis-as-a-pharmacological-target-in-therapy-resistant-solid-tumors