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. 2024 Oct 14;15(1):556.
doi: 10.1007/s12672-024-01433-y.

AURKA inhibition shows promise as a therapeutic strategy for ARID1A-mutant colorectal cancer

Rong-Sheng Qin  1 , Chun-Tao Li  2 , Fei Chen  1 , Shu Luo  1 , Chao Wang  1 , Jie Li  3 , Shan Xu  4   5 , MingWei Kang  6 , Hao-Wen Hu  7
Affiliations

AURKA inhibition shows promise as a therapeutic strategy for ARID1A-mutant colorectal cancer

Rong-Sheng Qin et al. Discov Oncol. .

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.

Keywords: ARID1A; AURKA; Colorectal cancer; Ex vivo; SWI/SNF.

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Conflict of interest statement

The authors declare no competing interests.

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Effect of AURKAi in CRC patients’ samples. A: illustration of immunohistochemistry (IHC) results showing the presence or absence of ARID1A expression in CRC clinical tumor. B: evaluation of the impact of the AURKAi alisertib on ex vivo CRC patient cells using the ATP-Tumor Chemosensitivity Assay. The assay measured ATP activity in ex vivo cells treated with alisertib at concentrations ranging from 0 to 10 nM in CRC patient cells with ( +) and without (-) ARID1A expression. X-axis is the test drug concentration percentage, and the Y-axis is the tumor growth inhibition percentage. C: results of the colony formation assay of ARID1A + and ARID1A—Ex Vivo CRC cells in 20 nM alisertib; D: percentage of colonies formed of ARID1A + and ARID1A—Ex Vivo CRC cells in 20 nM alisertib. E: results of the colony formation assay of ARID1A + and ARID1A—Ex Vivo CRC cells in 35 nM alisertib; F: percentage of colonies formed of ARID1A + and ARID1A—Ex Vivo CRC cells in 35 nM alisertib
Fig. 2
Fig. 2
Effects of AURKAi on Cell Cycle Arrest and apoptosis in ARID1A- CRC patients’ samples. A: effect of AURKAi on cell cycle progression; B: effect of AURKAi on apoptosis
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