Open Access
REVIEW
Aldo-keto reductases: Role in cancer development and theranostics
SIDDAVARAM NAGINI1, PRATHAP REDDY KALLAMADI2, KRANTHI KIRAN KISHORE TANAGALA3, GEEREDDY BHANUPRAKASH REDDY2,*
1 World Neem Organization, Mumbai, 400101, India
2 Department of Biochemistry, ICMR-National Institute of Nutrition, Hyderabad, 500007, India
3 Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, 10032, USA
* Corresponding Author: GEEREDDY BHANUPRAKASH REDDY. Email: 
,
Oncology Research https://doi.org/10.32604/or.2024.049918
Received 22 January 2024; Accepted 08 May 2024; Published online 11 June 2024
Abstract
Aldo-keto reductases (AKRs) are a superfamily of enzymes that play crucial roles in various cellular processes, including the metabolism of xenobiotics, steroids, and carbohydrates. A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various cancers. AKRs are aberrantly expressed in a wide range of malignant tumors. Dysregulated expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to chemoresistance. AKRs have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and progression. Inhibition of aldose reductase (AR), either alone or in combination with chemotherapeutic drugs, has evolved as a pragmatic therapeutic option for cancer. Several classes of synthetic aldo-keto reductase (AKR) inhibitors have been developed as potential anticancer agents, some of which have shown promise in clinical trials. Many AKR inhibitors from natural sources also exhibit anticancer effects. Small molecule inhibitors targeting specific AKR isoforms have shown promise in preclinical studies. These inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to chemotherapy. In this review, we discuss the physiological functions of human AKRs, the aberrant expression of AKRs in malignancies, the involvement of AKRs in the acquisition of cancer hallmarks, and the role of AKRs in oncogenic signaling, and drug resistance. Finally, the potential of aldose reductase inhibitors (ARIs) as anticancer drugs is summarized.
Keywords
Aldo-keto reductases (AKRs); Aldo-keto reductase (AKR) inhibitors; Cancer; Drug-resistance; Xenobiotics
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