Research Topic

Aldehyde Dehydrogenase in Clinical Settings: Potential Biomarker and Therapeutic Target in Solid Tumors

About this Research Topic

Aldehyde dehydrogenase (ALDH) is an enzyme that regulates important metabolic processes within cells through oxidation of aldehydes to carboxylic acids and that is required for the biosynthesis of retinoic acid. ALDH activity is involved in drug resistance, especially in cancer stem cells (CSCs). Although it is found in stem cells, CSCs, and progenitor cells, ALDH has been successfully used to identify and isolate cell populations with CSC properties from different tumor-type origins. Several oncology studies show that high activity of ALDH selects for tumor cells with increased aggressiveness and uncontrolled proliferation. Furthermore, recent studies indicate that the role of ALDH in metastasis is dependent on the cellular context and the different isoforms of the enzyme itself. ALDH1A1 and ALDH1A3 are the two isoforms most commonly associated with hematopoietic and solid tumors, and they exhibit cellular phenotypes specific to certain cancers. For example, ALDH1A1 and ALDH1A3 play an important role in lung and breast cancer cell migration and invasion, although the mechanisms underlying this behavior have not been well established.


Recent data indicate that ALDH is a determinant of cancer patient outcome since it is associated with CSCs. Moreover, cancer cell-acquired drug resistance is associated with the transcriptional activation of ALDH1 expression. In the past 10 years, the isoenzyme ALDH1A1 has been used as a marker of CSCs. However, the mechanisms underlying the effects of ALDHs in CSC maintenance and progression remain unclear. In addition to its potential role in tumor progression through CSCs, ALDH might also be a potential biomarker for circulating tumor cells (CTCs) and disseminated tumor cells (DTCs). The detection of CTCs in blood and DTCs in bone marrow has been associated with clinically relevant metastasis and an unfavorable outcome in a subgroup of solid tumors. It has been hypothesized that CTCs and/or DTCs might carry small populations of cells with an enhanced capacity to initiate tumor progression and favor metastasis, even if this mechanism is not fully exploited. 


ALDH was associated with several solid tumors, but it has not been validated as a prognostic biomarker and/or therapeutic target in the clinical setting. Also, further studies on the therapeutic effects of ALDH isoenzyme inhibitors in CTCs, DTCs, and metastatic and migratory activity are necessary. With this Research Topic in Frontiers in Medicine, we aim to collect clinical and preclinical studies which will help to understand the potential of ALDH in tumor therapy and prognosis.

Welcome themes include, but they are not limited to, the following:

• ALDH activity in the systemic circulation, which will help identify a correlation between ALDH activity and metastasis
• The use of ALDH as a biomarker in the identification of tumor cells
• The use of ALDH as a therapeutic target
• The use of ALDH as a prognostic factor


Keywords: ALDH, CTC, CSCs, marker, metastasis, cancer, NSCLC


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Aldehyde dehydrogenase (ALDH) is an enzyme that regulates important metabolic processes within cells through oxidation of aldehydes to carboxylic acids and that is required for the biosynthesis of retinoic acid. ALDH activity is involved in drug resistance, especially in cancer stem cells (CSCs). Although it is found in stem cells, CSCs, and progenitor cells, ALDH has been successfully used to identify and isolate cell populations with CSC properties from different tumor-type origins. Several oncology studies show that high activity of ALDH selects for tumor cells with increased aggressiveness and uncontrolled proliferation. Furthermore, recent studies indicate that the role of ALDH in metastasis is dependent on the cellular context and the different isoforms of the enzyme itself. ALDH1A1 and ALDH1A3 are the two isoforms most commonly associated with hematopoietic and solid tumors, and they exhibit cellular phenotypes specific to certain cancers. For example, ALDH1A1 and ALDH1A3 play an important role in lung and breast cancer cell migration and invasion, although the mechanisms underlying this behavior have not been well established.


Recent data indicate that ALDH is a determinant of cancer patient outcome since it is associated with CSCs. Moreover, cancer cell-acquired drug resistance is associated with the transcriptional activation of ALDH1 expression. In the past 10 years, the isoenzyme ALDH1A1 has been used as a marker of CSCs. However, the mechanisms underlying the effects of ALDHs in CSC maintenance and progression remain unclear. In addition to its potential role in tumor progression through CSCs, ALDH might also be a potential biomarker for circulating tumor cells (CTCs) and disseminated tumor cells (DTCs). The detection of CTCs in blood and DTCs in bone marrow has been associated with clinically relevant metastasis and an unfavorable outcome in a subgroup of solid tumors. It has been hypothesized that CTCs and/or DTCs might carry small populations of cells with an enhanced capacity to initiate tumor progression and favor metastasis, even if this mechanism is not fully exploited. 


ALDH was associated with several solid tumors, but it has not been validated as a prognostic biomarker and/or therapeutic target in the clinical setting. Also, further studies on the therapeutic effects of ALDH isoenzyme inhibitors in CTCs, DTCs, and metastatic and migratory activity are necessary. With this Research Topic in Frontiers in Medicine, we aim to collect clinical and preclinical studies which will help to understand the potential of ALDH in tumor therapy and prognosis.

Welcome themes include, but they are not limited to, the following:

• ALDH activity in the systemic circulation, which will help identify a correlation between ALDH activity and metastasis
• The use of ALDH as a biomarker in the identification of tumor cells
• The use of ALDH as a therapeutic target
• The use of ALDH as a prognostic factor


Keywords: ALDH, CTC, CSCs, marker, metastasis, cancer, NSCLC


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

14 May 2021 Abstract
11 September 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

14 May 2021 Abstract
11 September 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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