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Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets
David W Clark1, Komaraiah Palle1
1Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama 36604, USA.
Abstract:
Resistance to current chemotherapeutic or radiation-based cancer treatment strategies is a serious concern. Cancer stem cells (CSCs) are typically able to evade treatment and establish a recurrent tumor or metastasis, and it is these that lead to the majority of cancer deaths. Therefore, a major current goal is to develop treatment strategies that eliminate the resistant CSCs as well as the bulk tumor cells in order to achieve complete disease clearance. Aldehyde dehydrogenases (ALDHs) are important for maintenance and differentiation of stem cells as well as normal development. There is expanding evidence that ALDH expression increases in response to therapy and promotes chemoresistance and survival mechanisms in CSCs. This perspective will discuss a paper by Cojoc and colleagues recently published in Cancer Research, that indicates ALDHs play a key role in resistance to radiation therapy and tumor recurrence in prostate cancer. The authors suggest that ALDHs are a potential therapeutic target for treatment prostate cancer patients to limit radiation resistance and disease recurrence. The findings are consistent with work from other cancers showing ALDHs are major contributors of CSC signaling and resistance to anti-cancer treatments. This perspective will address representative work concerning the validity of ALDH and the associated retinoic acid signaling pathway as chemotherapeutic targets for prostate as well as other cancers.
Insights
Cancer stem cells (CSCs) resist treatment, causing recurrence. Aldehyde dehydrogenases (ALDHs) drive this resistance, suggesting ALDHs are a key therapeutic target for improving cancer treatment outcomes.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
- Molecular Therapeutics
Background:
- Treatment resistance in cancer, particularly by cancer stem cells (CSCs), leads to tumor recurrence and metastasis, contributing significantly to cancer mortality.
- Aldehyde dehydrogenases (ALDHs) are crucial for stem cell maintenance and differentiation, with increasing evidence linking their expression to therapy resistance and CSC survival.
Purpose of the Study:
- To discuss research indicating aldehyde dehydrogenases (ALDHs) play a critical role in prostate cancer resistance to radiation therapy and subsequent tumor recurrence.
- To explore the potential of targeting ALDHs as a therapeutic strategy to overcome treatment resistance and prevent disease recurrence in prostate cancer and other malignancies.
Main Methods:
- Discussion of a study by Cojoc et al. published in Cancer Research.
- Review of existing literature on ALDH expression, CSC signaling, and therapeutic targeting in various cancers.
- Analysis of the retinoic acid signaling pathway in conjunction with ALDH as a potential therapeutic target.
Main Results:
- Evidence suggests ALDHs are key mediators of resistance to radiation therapy in prostate cancer.
- Elevated ALDH expression is associated with tumor recurrence and CSC survival mechanisms.
- Findings align with broader research implicating ALDHs in CSC-driven resistance across multiple cancer types.
Conclusions:
- Aldehyde dehydrogenases (ALDHs) represent a promising therapeutic target for overcoming resistance to radiation therapy and reducing recurrence in prostate cancer.
- Targeting ALDHs and associated signaling pathways, such as the retinoic acid pathway, may offer a viable strategy for improving treatment efficacy in various cancers.
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