ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review).

The expression of cytosolic aldehyde dehydrogenases (ALDHs), which mediate the last step in the pathway of the synthesis of all-trans retinoic acid, is dysregulated in various types of human cancer, and has been associated with the development of cancer stem cells (CSCs) in solid tumors and hematological malignancies. CSCs are considered a minor fraction of cancer cells with the capacity to initiate neoplastic tumors. ALDH1A1 serves a crucial role in the emergence of the CSC phenotype, induces the malignant behavior of cancer cells and promotes treatment resistance. Notably, ALDH1A1-induced therapy resistance is not exclusive to just one group of drugs, but affects diverse types of drugs that use different mechanisms to kill cells. This diversity of drug resistance-inducing effects is associated with the stemness-supporting functions of ALDH1A1. The inhibition of ALDH1A1 activity using chemicals or the depletion of ALDH1A1 via genetic approaches, such as the use of small interfering RNA, can overcome diverse pathways of therapy resistance. In the context of breast cancer, it is critical that only a fraction of malignant cells are expected to manifest stem-like features, which include increased expression of ALDH1A1. From the angle of disease prognosis, the extent of the association of ALDH1A1 with increased malignant behavior and drug resistance remains to be determined through the application of cutting-edge methods that detect the expression of tracked biomarkers within tumors.