The role of aldehyde dehydrogenase (ALDH) in cancer drug resistance

Januchowski, Radosław; Wójtowicz, Karolina; Zabel, Maciej

doi:10.1016/j.biopha.2013.04.005

Cited by 175 publications

(148 citation statements)

References 159 publications

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“…According to CSCs theory of drug resistance development in tumors CSCs characterized among others by high expression level of drug transporters like P-gp and BCRP and other cells protecting mechanism are responsible for development of drug resistance (35). The universal marker of CSCs from different solid tumors is expression of ALDH1A1 gene (46).…”

Section: Discussionmentioning

confidence: 99%

“…According to CSCs theory of drug resistance development small population of cells is resistance to chemotherapy and after exposure to drugs these cells survive (35). Thus, in W1 cell line the up-regulation of ALDH1A1 can result not only from increased expression but also from changes of proportion between CSCs and other cells population.…”

Section: Discussionmentioning

confidence: 99%

“…These cells are characterized, among others, by high expression level of aldehyde dehydrogenase-1A1 (ALDH1A1) as well as high levels of expression of drug transporters like P-gp or BCRP (35). An increased number of ALDH1A1-positive cells was also reported in ovarian cancer and ovarian cancer cell lines and correlated with cisplatin (CIS), paclitaxel (PAC) and TOP resistance (36)(37)(38).…”

Section: Abstract Background: Low Effectiveness Of Chemotherapy In Omentioning

confidence: 99%

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New and Old Genes Associated with Topotecan Resistance Development in Ovarian Cancer Cell Lines

2017

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Abstract Background: Low Effectiveness Of Chemotherapy In Omentioning

confidence: 99%

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New and Old Genes Associated with Topotecan Resistance Development in Ovarian Cancer Cell Lines

2017

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“…ALDH has been proposed as a prognostic marker for many cancers including lung (45), breast (46), ovarian (47), pancreatic (24), and colon (48). There are many excellent recent reviews of ALDHs in cancer and CSCs (6,(49)(50)(51)(52) and these topics will not be discussed in detail here. ALDH has been most extensively studied in breast cancer where it correlates with tumor grade, ER negativity, HER2 positivity and poor patient survival (44,53,54).…”

Section: Figurementioning

confidence: 99%

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

2016

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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

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“…ALDH (aldehyde dehydrogenase) activity, often measured via ALDEFLUOR assay, has been successfully used as a marker to enrich CSC populations 11,[17][18][19][20][21][22] in a variety of cancers including human melanoma 23 and head and neck squamous cell cancer. 18 We characterized CSC-enriched populations in 2 histologically distinct murine tumors (melanoma D5 and squamous cell cancer SCC7) and evaluated their immunogenicity by administering CSC-based vaccines in 2 genetically different syngeneic immunocompetent hosts followed by tumor challenge.…”

Section: Introductionmentioning

confidence: 99%

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

et al. 2015

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Keywords: antitumor immunity, cancer stem cell, dendritic cell, metastasis, vaccine Abbreviations: ALDH, aldehyde dehydrogenase; CSC, cancer stem cell; CSC-DC, CSC lysate-pulsed dendritic cell; DC, dendritic cell; H-DC, heterogeneous, unsorted tumor cell lysate-pulsed dendritic cell; RT, radiation therapy; qRT-PCR, real time quantitative PCR.The inability to target cancer stem cells (CSC) may be a significant factor contributing to treatment failure. We have developed a strategy to target the CSC populations in melanoma and squamous cell carcinoma using CSC lysate-pulsed dendritic cells (DCs). The CSC-DC vaccine was administered in the adjuvant setting after localized radiation therapy of established tumors. Using mouse models we demonstrated that DCs pulsed with CSCs enriched by virtue of their expression of the CSC marker ALDH (termed CSC-DC) significantly inhibited tumor growth, reduced development of pulmonary metastases and prolonged survival. The effect was associated with downregulation of chemokine (C-C motif) receptors CCR7 and CCR10 in tumor cells and decreased expression of the chemokine (C-C motif) ligands CCL21, CCL27 and CCL28 in lung tissue. The CSC-DC vaccine significantly reduced ALDH high CSC frequency in primary tumors. Direct targeting of CSCs was demonstrated by the specific binding of IgG produced by ALDH high CSC-DC vaccineprimed B cells to ALDH high CSCs, resulting in lysis of these target CSCs in the presence of complement. These data suggest that the CSC-DC vaccine approach may be useful in the adjuvant setting where local and systemic relapse are high after conventional treatment of cancers.

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The role of aldehyde dehydrogenase (ALDH) in cancer drug resistance

Cited by 175 publications

References 159 publications

New and Old Genes Associated with Topotecan Resistance Development in Ovarian Cancer Cell Lines

New and Old Genes Associated with Topotecan Resistance Development in Ovarian Cancer Cell Lines

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

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