What is it about?
The objective of our current research article is to investigate whether ferroptosis, an iron-dependent form of cell death, may serve as an alternative therapeutic option against biliary tract cancer. To this end, we tested the effect of six established ferroptosis inducers, namely Brequinar, FIN56, FINO2, iFSP1, IKE and RSL3, on 11 biliary tract cancer cell lines. Our findings indicate that ferroptosis inducers, including IKE and RSL3, can significantly decrease cell viability. Moreover, our results demonstrate that ferroptosis is the dominant form of cell death involved in this decline of viability, in addition to apoptosis and necroptosis. Finally, our results suggest that the efficacy of these ferroptosis inducers correlates with the expression of CD71 and SLC7A11, two well-known pathway regulators of ferroptosis.
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Why is it important?
The primary objective of this study is to identify effective therapeutic strategies for biliary tract cancer. Due to the nonspecific nature of its symptoms, this disease is frequently diagnosed at an advanced stage, rendering it challenging to treat. Furthermore, current therapeutic approaches, including cisplatin and gemcitabine, often encounter resistance, limiting their efficacy. Ferroptosis, a non-apoptotic, ROS- and iron-dependent form of cell death, represents a promising avenue for cancer treatment. The current data regarding ferroptosis in biliary tract cancer is limited, and thus, the objective of this study was to investigate the effect of this type of cell death in this disease.
Perspectives
In my estimation, this research article represents a comprehensive overview of the impact of ferroptosis on biliary tract cancer cells. Notably, it demonstrates that ferroptosis is a dominant, yet not exclusive, type of cell death involved in the decline of cell viability. It prompts the question of whether there is a convergence between ferroptosis, apoptosis, and necroptosis. Furthermore, it is noteworthy that the efficacy of certain substances is contingent upon the expression of a transferrin receptor and a cystine-glutamate antiporter. It would be of interest to examine the expression of these proteins in biliary tract cancer patients, with a view to evaluating the potential utility of RSL3 and IKE, for instance. Further research is necessary to investigate the potential use of these substances in a clinical setting. For instance, it is necessary to determine the severity of the side effects of ferroptosis-inducing substances and the response of normal tissue to this treatment. Additionally, it is important to understand why there are currently no ferroptosis-inducing substances in clinical trials. Once these questions have been addressed, a clinical usage can be established.
Dino Bekric
Paracelsus Medizinische Privatuniversitat
Read the Original
This page is a summary of: The efficacy of ferroptosis-inducing compounds IKE and RSL3 correlates with the expression of ferroptotic pathway regulators CD71 and SLC7A11 in biliary tract cancer cells, PLoS ONE, April 2024, PLOS,
DOI: 10.1371/journal.pone.0302050.
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