Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer
Recent advances in molecular biology and the resultant identification of driver oncogenes have achieved major progress in precision medicine for non-small-cell lung cancer (NSCLC). v-Ki-ras2 Kirsten rat sarcoma viral oncogene (<i>KRAS</i>) is the most common driver in NSCLC, and targetin...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/23/5956 |
| _version_ | 1797508009656582144 |
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| author | Noriaki Sunaga Yosuke Miura Norimitsu Kasahara Reiko Sakurai |
| author_facet | Noriaki Sunaga Yosuke Miura Norimitsu Kasahara Reiko Sakurai |
| author_sort | Noriaki Sunaga |
| collection | DOAJ |
| description | Recent advances in molecular biology and the resultant identification of driver oncogenes have achieved major progress in precision medicine for non-small-cell lung cancer (NSCLC). v-Ki-ras2 Kirsten rat sarcoma viral oncogene (<i>KRAS</i>) is the most common driver in NSCLC, and targeting KRAS is considerably important. The recent discovery of covalent KRAS G12C inhibitors offers hope for improving the prognosis of NSCLC patients, but the development of combination therapies corresponding to tumor characteristics is still required given the vast heterogeneity of <i>KRAS</i>-mutated NSCLC. In this review, we summarize the current understanding of <i>KRAS</i> mutations regarding the involvement of malignant transformation and describe the preclinical and clinical evidence for targeting <i>KRAS</i>-mutated NSCLC. We also discuss the mechanisms of resistance to KRAS G12C inhibitors and possible combination treatment strategies to overcome this drug resistance. |
| first_indexed | 2024-03-10T04:56:31Z |
| format | Article |
| id | doaj.art-b94536a8b6574507969ca91fc30f8804 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:56:31Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b94536a8b6574507969ca91fc30f88042023-11-23T02:12:10ZengMDPI AGCancers2072-66942021-11-011323595610.3390/cancers13235956Targeting Oncogenic KRAS in Non-Small-Cell Lung CancerNoriaki Sunaga0Yosuke Miura1Norimitsu Kasahara2Reiko Sakurai3Department of Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi 371-8511, Gunma, JapanDepartment of Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi 371-8511, Gunma, JapanInnovative Medical Research Center, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi 371-8511, Gunma, JapanOncology Center, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi 371-8511, Gunma, JapanRecent advances in molecular biology and the resultant identification of driver oncogenes have achieved major progress in precision medicine for non-small-cell lung cancer (NSCLC). v-Ki-ras2 Kirsten rat sarcoma viral oncogene (<i>KRAS</i>) is the most common driver in NSCLC, and targeting KRAS is considerably important. The recent discovery of covalent KRAS G12C inhibitors offers hope for improving the prognosis of NSCLC patients, but the development of combination therapies corresponding to tumor characteristics is still required given the vast heterogeneity of <i>KRAS</i>-mutated NSCLC. In this review, we summarize the current understanding of <i>KRAS</i> mutations regarding the involvement of malignant transformation and describe the preclinical and clinical evidence for targeting <i>KRAS</i>-mutated NSCLC. We also discuss the mechanisms of resistance to KRAS G12C inhibitors and possible combination treatment strategies to overcome this drug resistance.https://www.mdpi.com/2072-6694/13/23/5956v-Ki-ras2 Kirsten rat sarcoma viral oncogenenon-small-cell lung cancercovalent KRAS G12C inhibitordrug resistancecombination therapy |
| spellingShingle | Noriaki Sunaga Yosuke Miura Norimitsu Kasahara Reiko Sakurai Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer Cancers v-Ki-ras2 Kirsten rat sarcoma viral oncogene non-small-cell lung cancer covalent KRAS G12C inhibitor drug resistance combination therapy |
| title | Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer |
| title_full | Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer |
| title_fullStr | Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer |
| title_full_unstemmed | Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer |
| title_short | Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer |
| title_sort | targeting oncogenic kras in non small cell lung cancer |
| topic | v-Ki-ras2 Kirsten rat sarcoma viral oncogene non-small-cell lung cancer covalent KRAS G12C inhibitor drug resistance combination therapy |
| url | https://www.mdpi.com/2072-6694/13/23/5956 |
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