2017 Fiscal Year Final Research Report
Novel treatment strategy based on amino acid metabolism of colorectal cancer
| Project/Area Number |
16K19918
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Research Collaborator |
KAWADA Kenji 京都大学, 大学院医学研究科, 客員研究員 (90322651)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 大腸癌 / FDG-PET検査 / KRAS遺伝子 / 糖代謝 |
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| Outline of Final Research Achievements |
A number of studies have shown that KRAS mutations in colorectal cancer (CRC) result in the lack of response to anti-EGFR-based therapy. Using CE/MS metabolomic analysis, We found that KRAS mutation in CRC caused alteration in amino acid metabolism. We demonstrated that the expression of asparagine synthetase (ASNS), an enzyme that synthesizes asparagine from aspartate, was upregulated by mutated KRAS. Importantly, we demonstrated that KRAS-mutant CRC cells could become adaptive to glutamine depletion through asparagine biosynthesis by ASNS, and that asparagine addition could rescue the inhibited growth and viability of cells grown under the glutamine-free condition in vitro. Combination of L-asparaginase plus rapamycin markedly suppressed the growth of KRAS-mutant CRC xenografts in vivo,ASNS might be a novel therapeutic target against CRCs with mutated KRAS.
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| Free Research Field |
消化器外科
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