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On ATG4B as Drug Target for Treatment of Solid Tumours-The Knowns and the Unknowns
Alexander Agrotis1, Robin Ketteler1
1MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
Abstract:
Autophagy is an evolutionary conserved stress survival pathway that has been shown to play an important role in the initiation, progression, and metastasis of multiple cancers; however, little progress has been made to date in translation of basic research to clinical application. This is partially due to an incomplete understanding of the role of autophagy in the different stages of cancer, and also to an incomplete assessment of potential drug targets in the autophagy pathway. While drug discovery efforts are on-going to target enzymes involved in the initiation phase of the autophagosome, e.g., unc51-like autophagy activating kinase (ULK)1/2, vacuolar protein sorting 34 (Vps34), and autophagy-related (ATG)7, we propose that the cysteine protease ATG4B is a bona fide drug target for the development of anti-cancer treatments. In this review, we highlight some of the recent advances in our understanding of the role of ATG4B in autophagy and its relevance to cancer, and perform a critical evaluation of ATG4B as a druggable cancer target.
Insights
Autophagy, a cellular process, is crucial in cancer. Targeting the cysteine protease ATG4B offers a promising strategy for developing novel anti-cancer drugs, moving research towards clinical application.
Area of Science:
- Molecular Biology
- Oncology
- Cellular Biology
Background:
- Autophagy is a conserved stress response pathway implicated in cancer initiation, progression, and metastasis.
- Translating autophagy research into clinical cancer treatments remains limited due to incomplete understanding of its role and drug targets.
- Current drug discovery focuses on early autophagy initiation enzymes like ULK1/2, Vps34, and ATG7.
Purpose of the Study:
- To review recent advances in understanding the role of ATG4B in autophagy and cancer.
- To critically evaluate ATG4B as a druggable target for anti-cancer therapies.
Main Methods:
- Literature review of recent research on ATG4B function in autophagy.
- Analysis of ATG4B's relevance and potential as a cancer drug target.
Main Results:
- ATG4B plays a significant role in the autophagy pathway.
- Recent findings highlight ATG4B's involvement in various stages of cancer development.
- ATG4B presents a viable target for anti-cancer drug development.
Conclusions:
- ATG4B is a promising and druggable target for anti-cancer drug development.
- Further research into ATG4B could accelerate clinical translation of autophagy-based cancer therapies.
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