Calpain 2 promotes Lenvatinib resistance and cancer stem cell traits via both proteolysis-dependent and independent approach in hepatocellular carcinoma
2024

Calpain 2 and Lenvatinib Resistance in Liver Cancer

Sample size: 12 publication 10 minutes Evidence: moderate

Author Information

Author(s): Ma Xiaolu, Zhou Kaixia, Yan Tianqing, Hu Ling, Xie Suhong, Zheng Hui, Tong Ying, Zhang Heng, Wang Yanchun, Gong Zhiyun, Chen Cuncun, Tian Yanan, Guo Lin, Lu Renquan

Primary Institution: Fudan University, Shanghai, China

Hypothesis

Calpain 2 is a key regulator of Lenvatinib resistance and cancer stem cell traits in hepatocellular carcinoma.

Conclusion

Calpain 2 promotes Lenvatinib resistance through both enzyme-dependent and independent mechanisms.

Supporting Evidence

  • Calpain 2 expression was significantly higher in Lenvatinib-resistant HCC cell lines.
  • Knocking down Calpain 2 sensitized HCC cells to Lenvatinib treatment.
  • Overexpression of Calpain 2 conferred resistance to Lenvatinib in sensitive HCC cell lines.
  • Calpain 2 was identified as a novel key member of the calpain family for mediating Lenvatinib resistance.
  • Calpain 2 promoted cancer stem cell traits in HCC cells.
  • Calpain 2's function involved both enzyme-dependent and independent mechanisms.

Takeaway

Calpain 2 helps liver cancer cells resist a drug called Lenvatinib, making it harder to treat the cancer.

Methodology

The study used bioinformatic analysis, in vitro and in vivo experiments to investigate the role of Calpain 2 in Lenvatinib resistance.

Potential Biases

Potential bias in patient enrollment and individual heterogeneity affecting treatment response.

Limitations

The study was retrospective with a small sample size and short follow-up time.

Participant Demographics

12 advanced hepatocellular carcinoma patients who received Lenvatinib treatment.

Statistical Information

P-Value

0.06

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/s43556-024-00242-7

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