Pharmacogenomic Analysis Reveals CCNA2 as a Predictive Biomarker of Sensitivity to Polo-Like Kinase I Inhibitor in Gastric Cancer
| Autor: | Joo Young Lee, Hyun Seok Kim, Oh Sejin, Chae Eun Lee, Yunji Lee, Hakhyun Kim, Sang Bum Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.disease_cause PLK1 lcsh:RC254-282 Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine BI-2536 medicine KRAS Mitotic catastrophe business.industry gastric cancer Cancer Volasertib CCNA2 medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Cancer cell polo-like kinase 1 Cancer research Biomarker (medicine) business Cyclin A2 |
| Zdroj: | Cancers Volume 12 Issue 6 Cancers, Vol 12, Iss 1418, p 1418 (2020) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12061418 |
| Popis: | Despite recent innovations and advances in early diagnosis, the prognosis of advanced gastric cancer remains poor due to a limited number of available therapeutics. Here, we employed pharmacogenomic analysis of 37 gastric cancer cell lines and 1345 small-molecule pharmacological compounds to investigate biomarkers predictive of cytotoxicity among gastric cancer cells to the tested drugs. We discovered that expression of CCNA2, encoding cyclin A2, was commonly associated with responses to polo-like kinase 1 (PLK1) inhibitors (BI-2536 and volasertib). We also found that elevated CCNA2 expression is required to confer sensitivity to PLK1 inhibitors through increased mitotic catastrophe and apoptosis. Further, we demonstrated that CCNA2 expression is elevated in KRAS mutant gastric cancer cell lines and primary tumors, resulting in an increased sensitivity to PLK1 inhibitors. Our study suggests that CCNA2 is a novel biomarker predictive of sensitivity to PLK1 inhibitors for the treatment of advanced gastric cancer, particularly cases carrying KRAS mutation. |
| Databáze: | OpenAIRE |
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