AKR1C1 overexpression

It has been approved as a first-line drug after sorafenib in hepatocellular carcinoma (HCC). Online data analysis of LR cells showed significant differences in the immune microenvironment and drug sensitivity compared with their parental counterparts. Taken together, AKR1C1 may serve as a candidate therapeutic target for LR liver cancer patients.

Aspirin, which is an AKR1C1 inhibitor, could help reduce the drug resistance caused by AKR1C1. After receiving THP treatment, the bladder cancer cell lines could upregulate the expression of the AKR1C1 gene through the ROS/KEAP1/NRF2 pathway, leading to resistance to THP treatment. Using tempol, which is an inhibitor of ROS, could prevent the upregulation of AKR1C1 expression.

Suppression of AKR1C1 by brusatol resulted in decreased progesterone catabolism and maintained potent progesterone to inhibit endometrial cancer growth...The authors found that brusatol, as a natural compound, suppresses progestin metabolism through regulating the NRF2-TET1-AKR1C1 pathway to sensitize precancerous/endometrial cancers to progestin and relieve progestin resistance. This study indicates that progestin combined with brusatol may enhance the treatment effects and that AKR1C1 expression patterns may serve as an important biomarker of progestin resistance in endometrial cancer.

Suppression of AKR1C1 by brusatol resulted in decreased progesterone catabolism and maintained potent progesterone to inhibit endometrial cancer growth...Aberrant overexpression of AKR1C1 was found in paired endometrial hyperplasia and cancer samples from the same individuals with progestin resistance, whereas attenuated or loss of AKR1C1 was observed in post-treatment samples with well progestin response as compared with paired pre-treatment tissues. Our findings suggest that AKR1C1 expression pattern may serve as an important biomarker of progestin resistance in endometrial cancer.

ZnS exerts an anticancer effect on HCC via inhibiting autophagy moderated by the AKR1C1-mediated JAK2/STAT3 pathway. ZnS and 3-MA exert a synergistic effect on inhibiting HCC.