AURKA inhibition shows promise as a therapeutic strategy for ARID1A-mutant colorectal cancer
Year: 2024
Type: article
Abstract: PURPOSE: Mutations in ARID1A frequently occur in colorectal cancer (CRC) cells. However, there are currently no clinical treatment options specifically addressing this aberration. The preliminary in vitro experiments revealed a synthetic lethal interaction between ARID1A and Aurora kinase A (AURKA) in colorectal cancer (CRC) cells. METHODS: We collected samples from 80 CRC patients and evaluated the efficacy of AURKA inhibitor (AURKAi) using the ATP-tumor chemosensitivity assay (ATP-TCA) on untreated ARID1A-proficient (ARID1A +) and ARID1A-deficient (ARID1A-) CRC patient samples. In addition, we validated this result by a clonogenic assay. Additionally, we examined the effects of AURKA inhibitors on cell cycle progression and apoptosis in ARID1A + and ARID1A- CRC patient samples using flow cytometry. RESULTS: The results showed that AURKAi selectively inhibited the growth of ARID1A- CRC cells. Furthermore, AURKA inhibitors significantly increased G2/M arrest and induced apoptosis in ARID1A- cells. CONCLUSION: We believe that AURKAi hold promise as potential therapeutics for ARID1A mutation colorectal cancer patients.
Source: Discover Oncology
Authors: Rong-Sheng Qin, Chun-Tao Li, Fei Chen, Shu Luo, Chao Wang, Jie Li, Shan Xu, MingWei Kang, Hao-Wen Hu
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,590
OpenAlex ID: W4403384357