Ferroptosis Plays a Pivotal Role in Activating and Modulating SpecificIntracellular Signaling Pathways Integrated into the TherapeuticManagement of Colorectal Cancer

Document Type : Review Article

Authors
1 Department of Basic Science, Faculty of Pharmacy and Pharmaceutical Science, Tehran Medical Science, Islamic Azad University, Tehran, Iran.
2 ollege of Pharmacy, Alnoor University, Mosul, Iraq.
3  Ahl Al Bayt University, Kerbala, Iraq.
4 College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
5 Pharmacy College, Al-Farahidi University, Iraq.
6 Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq.
7 Gilgamesh Ahliya University, Baghdad, Iraq.
8 Departments of Internal Medical, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
It is expected that the amount of recently diagnosed colon cancer cases will increase to around 3.2 million yearly
until 2040. Although early diagnostic procedures and management approaches have been improved, colorectal

cancer (CRC) treatment remains chal
lenging. There is an urgent need to discover new therapeutic agents to
enhance therapeutic strategies. Ferroptosis is distinguished as a mode of regulated cell death considered by iron
-
dependent lipid peroxidation. Contemporary investigations suggest that
induction of ferroptosis in CRC can
effectively target neoplastic cells that are resistant to alternative forms of cell death. This review has summarized

recent scientific work on the implications of ferroptosis in CRC treatment and highlights its underlyi
ng
molecular and biological mechanisms. While investigating its therapeutic potential, it shows the importance of

diverse modulators of ferroptosis, including the 7
-membered solute carrier family 11 or xCT (SLC7A11),
reactive oxygen species (ROS), glutathi
one (GSH), and iron in the context of CRC. Recent research has
identified specific pathways and compounds that can induce ferroptosis in CRC, such as apatinib and elesclimol,

which are involved in pivotal signaling cascades. Attenuation of proteins such as
splicing factor, arginine/serine
9 (SFRS9), and Tp53
-induced glycolysis and apoptosis regulator (TIGAR) may increase the sensitivity of CRC
cells to ferroptosis, thus suggesting promising therapeutic avenues. Compounds including IMCA and β
-elemene
have sh
own efficacy in inducing ferroptosis while minimizing toxicity to normal tissues, thereby demonstrating
their potential as therapeutic agents for CRC. Participating ferroptosis stimulator drugs with current treatment

regimens, such as cetuximab and aspirin
, may offer better treatment outcomes for CRC patients, especially those
presenting resistance to conventional therapies.
Keywords