A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRAS
Abstract The KRAS gene is frequently mutated in multiple cancer types, but it fell off the drug discovery radar for many years because of its inherent “undruggable” structure and undefined biological properties. As reported in the paper entitled “Suppression of KRas-mutant cancer through the combine...
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| Format: | Article |
| Language: | English |
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BMC
2016-10-01
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| Series: | Chinese Journal of Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40880-016-0154-7 |
| _version_ | 1831746177594294272 |
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| author | Xiufeng Pang Mingyao Liu |
| author_facet | Xiufeng Pang Mingyao Liu |
| author_sort | Xiufeng Pang |
| collection | DOAJ |
| description | Abstract The KRAS gene is frequently mutated in multiple cancer types, but it fell off the drug discovery radar for many years because of its inherent “undruggable” structure and undefined biological properties. As reported in the paper entitled “Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” in Nature Communications, we performed a synthetic lethal screening with a combinatorial strategy on a panel of clinical drugs; we found that combined inhibition of polo-like kinase 1 and RhoA/Rho kinase markedly suppressed tumor growth in mice. An increase in the expression of the tumor suppressor P21WAF1/CIP1 contributed to the synergistic mechanism of the combination therapy. These findings open a novel avenue for the treatment of KRAS-mutant lung cancer. |
| first_indexed | 2024-12-21T21:10:35Z |
| format | Article |
| id | doaj.art-779e4ba4ab8847efbf8488ed534a9c25 |
| institution | Directory Open Access Journal |
| issn | 1944-446X |
| language | English |
| last_indexed | 2024-12-21T21:10:35Z |
| publishDate | 2016-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Journal of Cancer |
| spelling | doaj.art-779e4ba4ab8847efbf8488ed534a9c252022-12-21T18:50:09ZengBMCChinese Journal of Cancer1944-446X2016-10-013511310.1186/s40880-016-0154-7A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRASXiufeng Pang0Mingyao Liu1Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal UniversityShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal UniversityAbstract The KRAS gene is frequently mutated in multiple cancer types, but it fell off the drug discovery radar for many years because of its inherent “undruggable” structure and undefined biological properties. As reported in the paper entitled “Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” in Nature Communications, we performed a synthetic lethal screening with a combinatorial strategy on a panel of clinical drugs; we found that combined inhibition of polo-like kinase 1 and RhoA/Rho kinase markedly suppressed tumor growth in mice. An increase in the expression of the tumor suppressor P21WAF1/CIP1 contributed to the synergistic mechanism of the combination therapy. These findings open a novel avenue for the treatment of KRAS-mutant lung cancer.http://link.springer.com/article/10.1186/s40880-016-0154-7Synthetic lethalityKRASPolo-like kinase 1RhoA/Rho kinaseCombination therapy |
| spellingShingle | Xiufeng Pang Mingyao Liu A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRAS Chinese Journal of Cancer Synthetic lethality KRAS Polo-like kinase 1 RhoA/Rho kinase Combination therapy |
| title | A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRAS |
| title_full | A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRAS |
| title_fullStr | A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRAS |
| title_full_unstemmed | A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRAS |
| title_short | A combination therapy for KRAS-mutant lung cancer by targeting synthetic lethal partners of mutant KRAS |
| title_sort | combination therapy for kras mutant lung cancer by targeting synthetic lethal partners of mutant kras |
| topic | Synthetic lethality KRAS Polo-like kinase 1 RhoA/Rho kinase Combination therapy |
| url | http://link.springer.com/article/10.1186/s40880-016-0154-7 |
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