Iranian Journal of Colorectal Research

Iranian Journal of Colorectal Research

Mitochondria-Targeted Radiosensitization in Colorectal Cancer: A Review

Document Type : Review Article

Author
khadijeh dizaji asl
Department of Histopathology and Anatomy, TaMS.C, Islamic Azad University, Tabriz, Iran
10.30476/acrr.2026.112142.1288
Abstract
Colorectal cancers (CRC) are the third most common malignancy worldwide. Resistance to conventional
treatments, along with their associated side effects, is a major cause of the high mortality rate in these cancers.
Recent evidence demonstrates that mitochondrial dysfunction plays an important role in tumor progression,
cancer stem cell (CSC) maintenance, and the development of treatment resistance. Targeting mitochondria
through genetic methods, pharmacological treatments, or manipulation of mitochondrial dynamics appears to
enhance the radiosensitivity of CRC. In this regard, mitochondrial metabolism, reactive oxygen species (ROS)
production, and apoptotic pathways are key determinants of radiation response. Pharmacological inhibition of
mitochondrial complexes, particularly complexes I and III, can increase oxidative stress and enhance cell death
following irradiation. Additionally, targeting mitochondrial dynamics by inducing excessive fission or inhibiting
fusion has shown synergistic effects with radiation therapy. Several novel agents, such as metformin, honokiol,
and certain small-molecule inhibitors, are currently under investigation for their radiosensitizing potential
in CRC models. However, challenges including tumor heterogeneity, optimal timing of administration, and
potential toxicity to normal tissues remain unresolved. This review provides an overview of the current state
of mitochondrial-targeted radiosensitization in CRC, with a particular focus on pharmacological inhibition of
mitochondria. The emerging paradigm of mitochondria-based radiosensitization offers a promising strategy to
overcome radioresistance in CRC patients; however, further investigations are required to achieve this goal.

Highlights

Khadijeh Dizaji Asl (Google Scholar)

Keywords
Colorectal Neoplasms
Radiation Tolerance
Mitochondria
Radiation-Sensitizing Agents
Neoplastic Stem Cells
Oxidative Stress
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