Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Ferroptosis is a regulated cell death pathway driven by iron-dependent lipid peroxidation.
• Key regulators include GPX4, ACSL4, and SLC7A11, influencing cell death and survival.
• Ferroptosis plays a complex role in cancer, potentially eliminating tumor cells or promoting resistance and metastasis.

Purpose of the Study:

• To systematically review ferroptosis mechanisms, its role in cancer, and interactions with the tumor microenvironment (TME).
• To analyze cancer type-specific ferroptosis sensitivity and evaluate clinical progress in ferroptosis-targeted therapies.
• To provide a framework for developing ferroptosis-targeted cancer therapies by addressing current research gaps.

Main Methods:

• Literature review and synthesis of existing research on ferroptosis.
• Analysis of molecular mechanisms, including GPX4, ACSL4, and SLC7A11.
• Evaluation of preclinical and clinical data on ferroptosis-targeting agents and delivery systems.

Main Results:

• Ferroptosis induction can eliminate cancer cells, but evasion contributes to drug resistance and metastasis.
• Emerging therapeutic strategies involve single agents, combination regimens, and nanocarrier systems.
• Preliminary data show tumor-suppressive signals in preclinical models for ferroptosis-targeted therapies.

Conclusions:

• Targeting ferroptosis is a promising avenue for anticancer drug development.
• Understanding ferroptosis-TME crosstalk and cancer-specific sensitivity is crucial for effective therapy.
• Addressing clinical translation barriers is essential for advancing ferroptosis-targeted cancer treatments.