Aldehyde dehydrogenase 1 family member A1 and Aldehyde dehydrogenase 1 family member A3 (ALDH1A1/ALDH1A3)

Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and member A3 (ALDH1A3) are cytosolic enzymes that catalyze the NAD+-dependent oxidation of aldehydes to their corresponding carboxylic acids [3, 7]. They are critical for the synthesis of retinoic acid, a key signaling molecule that regulates cell differentiation, proliferation, and embryonic development [9, 10]. In oncology, these isoforms are prominent markers and functional drivers of cancer stem cells (CSCs), contributing to tumor initiation, metastasis, and therapeutic resistance [2, 4]. They protect cancer cells by detoxifying chemotherapeutic agents like cyclophosphamide and by clearing reactive aldehydes produced during oxidative stress [14, 16]. High expression of ALDH1A1 and ALDH1A3 is associated with poor clinical outcomes in various malignancies, including breast cancer and glioblastoma [5, 12]. Targeting these enzymes aims to eradicate the CSC population and sensitize tumors to conventional treatments [1, 18]. However, therapeutic development must balance efficacy with potential safety concerns, such as the disruption of normal stem cell function and retinoic acid-mediated physiological processes [5, 10].

Other names

ALDH1ALDCALDH11PQR3RALDH1Retinal dehydrogenase 1ALDH6RALDH3Retinal dehydrogenase 3

Inhibition of ALDH enzymatic activity, leading to the accumulation of toxic aldehydes and reactive oxygen species (ROS), depletion of retinoic acid signaling, and sensitization of cancer stem cells to chemotherapy and radiation [2, 7, 16].