KRAS mutation in pancreatic cancer
Pancreatic cancer is a recalcitrant cancer with one of the lowest 5-year survival rates. A hallmark of pancreatic cancer is the prevalence of oncogenic mutation in the KRAS gene. The KRAS oncogene plays a critical role in the initiation and maintenance of pancreatic tumors and its signaling network...
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| Published in: | Seminars in oncology Vol. 48; no. 1; p. 10 |
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| Format: | Journal Article |
| Language: | English |
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United States
01.02.2021
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| ISSN: | 1532-8708, 1532-8708 |
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| Abstract | Pancreatic cancer is a recalcitrant cancer with one of the lowest 5-year survival rates. A hallmark of pancreatic cancer is the prevalence of oncogenic mutation in the KRAS gene. The KRAS oncogene plays a critical role in the initiation and maintenance of pancreatic tumors and its signaling network represents a major target for therapeutic intervention. A number of inhibitors have been developed against kinase effectors in various Ras signaling pathways. Their clinical activity, however, has been disappointing thus far. More recently, covalent inhibitors targeting the KRAS
oncoprotein have been developed. These inhibitors showed promising activity in KRAS
mutant pancreatic cancer in early clinical trials. This review will present an updated summary of our understanding of mutant KRAS function in pancreatic cancer and discuss therapeutic strategies that target oncogenic KRAS signaling in this disease. |
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| AbstractList | Pancreatic cancer is a recalcitrant cancer with one of the lowest 5-year survival rates. A hallmark of pancreatic cancer is the prevalence of oncogenic mutation in the KRAS gene. The KRAS oncogene plays a critical role in the initiation and maintenance of pancreatic tumors and its signaling network represents a major target for therapeutic intervention. A number of inhibitors have been developed against kinase effectors in various Ras signaling pathways. Their clinical activity, however, has been disappointing thus far. More recently, covalent inhibitors targeting the KRAS
oncoprotein have been developed. These inhibitors showed promising activity in KRAS
mutant pancreatic cancer in early clinical trials. This review will present an updated summary of our understanding of mutant KRAS function in pancreatic cancer and discuss therapeutic strategies that target oncogenic KRAS signaling in this disease. Pancreatic cancer is a recalcitrant cancer with one of the lowest 5-year survival rates. A hallmark of pancreatic cancer is the prevalence of oncogenic mutation in the KRAS gene. The KRAS oncogene plays a critical role in the initiation and maintenance of pancreatic tumors and its signaling network represents a major target for therapeutic intervention. A number of inhibitors have been developed against kinase effectors in various Ras signaling pathways. Their clinical activity, however, has been disappointing thus far. More recently, covalent inhibitors targeting the KRASG12C oncoprotein have been developed. These inhibitors showed promising activity in KRASG12C mutant pancreatic cancer in early clinical trials. This review will present an updated summary of our understanding of mutant KRAS function in pancreatic cancer and discuss therapeutic strategies that target oncogenic KRAS signaling in this disease.Pancreatic cancer is a recalcitrant cancer with one of the lowest 5-year survival rates. A hallmark of pancreatic cancer is the prevalence of oncogenic mutation in the KRAS gene. The KRAS oncogene plays a critical role in the initiation and maintenance of pancreatic tumors and its signaling network represents a major target for therapeutic intervention. A number of inhibitors have been developed against kinase effectors in various Ras signaling pathways. Their clinical activity, however, has been disappointing thus far. More recently, covalent inhibitors targeting the KRASG12C oncoprotein have been developed. These inhibitors showed promising activity in KRASG12C mutant pancreatic cancer in early clinical trials. This review will present an updated summary of our understanding of mutant KRAS function in pancreatic cancer and discuss therapeutic strategies that target oncogenic KRAS signaling in this disease. |
| Author | Luo, Ji |
| Author_xml | – sequence: 1 givenname: Ji surname: Luo fullname: Luo, Ji email: ji.luo@nih.gov organization: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD. Electronic address: ji.luo@nih.gov |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33676749$$D View this record in MEDLINE/PubMed |
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| Title | KRAS mutation in pancreatic cancer |
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