Modulations of ferroptosis in lung cancer therapy

ABSTRACT

Introduction

Ferroptosis is iron-dependent regulated cell death and is a field of research that has been rapidly growing in recent years. Many preclinical studies show therapeutic benefit of ferroptosis modulation in lung cancers. There are advancements using prognostic ferroptosis-related genes to directly predict outcomes in lung cancer. Targeted therapy using RNA and nanoparticle technology have also shown benefits in ferroptosis induction. Currently, there is limited comprehensive evaluation of how ferroptosis can be used in lung cancer therapy. Thus, the aim of this report is to build an overview of all data on ferroptosis modulation in lung cancer.

Areas covered

Ferroptotic cell death mechanisms and how ferroptosis is highly distinguished from other forms of cell death, offered insight on the modulations of ferroptosis in killing lung cancer cells in preclinical studies. Search databases included PubMed, Google scholar, and clinicaltrials.gov through the last 10 years.

Expert opinion

Ferroptosis modulation in lung cancer is a promising therapeutic option, but greater understanding and progression from primarily in vitro studies to animal studies and clinical trials is needed to substantiate its utilization in practice. Future strategies of using ferroptosis modulation adjuvant to first-line therapy may increase its effectiveness and overcome apoptosis-resistance cancers.

KEYWORDS:

• Ferroptosis
• lung cancer
• iron
• molecular mechanism
• targeted delivery
• nanoparticles
• lipid peroxidation

Article highlights

• Ferroptosis is an iron-dependent form of cell death and is very distinct from other cell death pathways

• GPX4 inactivation, glutathione depletion, iron accumulation, and lipid peroxidation are key mechanisms of ferroptosis

• Many preclinical, in vitro and in vivo studies show promising modulations of ferroptosis in lung cancer

• Prognostic models have been developed using ferroptosis-related genes (FRGs) and long non-coding RNAs (lncRNAs) to predict outcomes in lung cancer

• Targeted therapy using RNA and nanoparticle technology to induce ferroptosis shows promise in lung cancer through in vitro and in vivo studies

• Many promising therapeutic targets have been identified, including system Xc⁻ inhibition, GP4 inhibition, SLC7A11, FSP1, HO-1, GPX4, Nrf2, NCOA4

Reviewers disclosure statement

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Conflict of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.