Aldehyde Dehydrogenase-1A1 (ALDH1A1) - The Novel Regulator of Chemoresistance in Pancreatic Cancer Cells

Sep 21, 2026

A comprehensive review focuses on Aldehyde dehydrogenase-1A1 (ALDH1A1), an ALDH superfamily isozyme involved in key physiological and pathological processes. Chemotherapy is central for pancreatic cancer, yet chemoresistance drives treatment failure. Evidence indicates ALDH1A1 overexpression links to poor prognosis, tumor aggressiveness, and clinical chemoresistance. The review also examines how ALDH1A1 may influence cancer stem cell–like traits and clarifies the unclear molecular pathways governing chemoresistance development and prognostic relevance, aiming to consolidate clinical functions in pancreatic cancer.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Pancreatic cancer burden and biomarker limitations

ALDH1A1 biology and relevance to therapy resistance

ALDH isoenzymes and ALDH1A1 substrate specificity

Associations between ALDH1A1 expression and disease progression

ALDH1A1 as a regulator of chemoresistance and cancer stem cell development

Clinical functions and prognostic implications

Aldehyde Dehydrogenase-1A1 (ALDH1A1): The Novel Regulator of Chemoresistance in Pancreatic Cancer Cells Cancer Control Volume 31: 1–10 © The Author(s) 2024 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions) [DOI: 10.1177/10732748241305835](DOI: 10.1177/10732748241305835)[ ](DOI: 10.1177/10732748241305835)[journals.sagepub.com/home/ccx](journals.sagepub.com/home/ccx) Hong-Quan Duong, PhD 1 􀀁, Minh-Cong Hoang, MSc2, Thi-Hue Nguyen, MSc3, Phuong-Thoa Nguyen, MSc 1, Van-Thu Le, MSc 1, Thi-Nguyet Dao, MSc4, Van-Lang Ngo, MSc5, and The-Hung Dang, PhD 1 Abstract Aldehyde dehydrogenase-1A1 (ALDH1A1), a member of a superfamily of 19 isozymes, exhibits various biological functions and is involved in several important physiological and pathological processes, including those associated with various diseases including cancers such as pancreatic cancer. Chemotherapy is one of the most important strategies for the treatment of pancreatic cancer; however, the chemoresistance exhibited by pancreatic cancer cells is a leading cause of chemotherapy failure. It has been reported that overexpression of ALDH1A1 signiﬁcantly correlates with poor prognosis and tumor aggressiveness, and is clinically associated with chemoresistance. Additionally, ALDH1A1 may serve as a novel regulator for the diagnosis and prognosis of cancer resistance. In particular, ALDH1A1 can promote cancer progression by facilitating the manifestation of cancer stem cell properties. However, the molecular mechanism by which ALDH1A1 clinically regulates the development of chemoresistance, and its role in prognosis and cancer stem cells, including pancreatic cancer stem cells, remain unclear. Therefore, the current review aims to summarize the clinical functions of ALDH1A1 as a novel regulator of chemoresistance, prognosis, and cancer stem cell development in pancreatic cancer. Keywords aldehyde dehydrogenase-1A1, chemoresistance, pancreatic cancer cells, cancer drug resistance, cancer stem cells Received August 15, 2024. Received revised November 18, 2024. Accepted for publication November 20, 2024. Introduction Pancreatic cancer is one of the most dangerous solid malignancies, characterized by its aggressiveness and metastatic potential, with a ﬁve-year overall survival rate of just 12% .1,2 It remains as the fourth leading cause of cancer-related deaths globally, and is considered a silent disease due to the absence of early symptoms. As a result, it is often detected at a late stage, and is associated with high mortality, primarily due to lack of early biomarkers for detection and the resistance to traditional therapeutic regiments such as chemotherapy and radiotherapy.1-3 Several biomarkers have been proposed for the early detection of pancreatic cancer, including serum carbohydrate antigen (CA19-9),4,5 carcinoembryonic antigen (CEA),5 methylated DNA biomarkers (CD1D, KCNK12, CLEC11A, NDRG4, IKZF1, and PKRCB), and mutant KRAS.6 However, these markers still have signiﬁcant 1 Laboratory Center, Hanoi University of Public Health, Hanoi, Vietnam 2Laboratory Department, Yenphong Medical Center, Bacninh, Vietnam 3Laboratory Department, Bacgiang General Hospital, Bacgiang, Vietnam 4Pathology Department, Ducgiang General Hospital, Hanoi, Vietnam 5Faculty of Biomedical Sciences, Phenikaa University, Hanoi, Vietnam Corresponding Author: Hong-Quan Duong, Laboratory Center, Hanoi University of Public Health, 1A Duc Thang, Duc Thang, North Tu Liem, Hanoi 100000, Vietnam. Email: [dhq@huph.edu.vn](dhq@huph.edu.vn) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as sp

FAQs

What role does ALDH1A1 play in pancreatic cancer chemoresistance?

ALDH1A1 overexpression correlates with poor prognosis and tumor aggressiveness and is clinically associated with chemoresistance in pancreatic cancer cells.

Why is pancreatic cancer difficult to detect early and treat effectively?

It is characterized by aggressiveness and metastatic potential, often has no early symptoms, is diagnosed late, and lacks early biomarkers, contributing to high mortality and therapy resistance.

What is the focus of the review regarding ALDH1A1?

The review summarizes ALDH1A1’s clinical functions as a regulator of chemoresistance, prognosis, and cancer stem cell development, particularly in pancreatic cancer.

Sep 21, 2026

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