Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-A
Abstract Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with a poor prognosis. Compared to non-small cell lung cancer, IMA more frequently harbors KRAS mutations in the order p.G12V, p.G12D, and p.G12C. This report describes a patient with a KRAS p.G12C-mutant IMA tr...
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Nature Portfolio
2025-05-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00953-2 |
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| author | Hiraku Yanada Ryohei Yoshida Ryotaro Kida Kiichi Nitanai Maya Ikeda Kazunori Nagasue Taeka Naraoka Masashi Ueda Takashi Watanabe Ryota Shigaki Yasuhiro Umekage Yoshinori Minami Toshihiro Nagato Manami Hayashi Sayaka Yuzawa Mishie Tanino Takaaki Sasaki |
| author_facet | Hiraku Yanada Ryohei Yoshida Ryotaro Kida Kiichi Nitanai Maya Ikeda Kazunori Nagasue Taeka Naraoka Masashi Ueda Takashi Watanabe Ryota Shigaki Yasuhiro Umekage Yoshinori Minami Toshihiro Nagato Manami Hayashi Sayaka Yuzawa Mishie Tanino Takaaki Sasaki |
| author_sort | Hiraku Yanada |
| collection | DOAJ |
| description | Abstract Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with a poor prognosis. Compared to non-small cell lung cancer, IMA more frequently harbors KRAS mutations in the order p.G12V, p.G12D, and p.G12C. This report describes a patient with a KRAS p.G12C-mutant IMA treated with sotorasib. To date, no studies have investigated the therapeutic efficacy or resistance mechanisms of sotorasib in IMA. The patient was treated with carboplatin and pemetrexed, followed by sotorasib upon disease progression. While the primary lung lesions responded well, metastatic thoracic lymph node lesions continued to increase. A pathological autopsy was performed with the family’s consent to investigate potential resistance mechanisms. RNA sequencing and additional analyses revealed increased VEGF-A expression in metastatic lymph node lesions, suggesting a role in sotorasib resistance. These findings provide insights into the potential molecular mechanisms underlying treatment resistance in KRAS p.G12C-mutant IMA. |
| format | Article |
| id | doaj-art-d730aad7f527446c8ab6a6a8a81ab4e8 |
| institution | OA Journals |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-d730aad7f527446c8ab6a6a8a81ab4e82025-08-20T02:39:04ZengNature Portfolionpj Precision Oncology2397-768X2025-05-01911610.1038/s41698-025-00953-2Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-AHiraku Yanada0Ryohei Yoshida1Ryotaro Kida2Kiichi Nitanai3Maya Ikeda4Kazunori Nagasue5Taeka Naraoka6Masashi Ueda7Takashi Watanabe8Ryota Shigaki9Yasuhiro Umekage10Yoshinori Minami11Toshihiro Nagato12Manami Hayashi13Sayaka Yuzawa14Mishie Tanino15Takaaki Sasaki16Department of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityDepartment of Pathology, Asahikawa Medical UniversityDepartment of Diagnostic Pathology, Asahikawa Medical University HospitalDepartment of Diagnostic Pathology, Asahikawa Medical University HospitalDepartment of Diagnostic Pathology, Asahikawa Medical University HospitalDepartment of Internal Medicine, Division of Respiratory Medicine and Neurology, Asahikawa Medical UniversityAbstract Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with a poor prognosis. Compared to non-small cell lung cancer, IMA more frequently harbors KRAS mutations in the order p.G12V, p.G12D, and p.G12C. This report describes a patient with a KRAS p.G12C-mutant IMA treated with sotorasib. To date, no studies have investigated the therapeutic efficacy or resistance mechanisms of sotorasib in IMA. The patient was treated with carboplatin and pemetrexed, followed by sotorasib upon disease progression. While the primary lung lesions responded well, metastatic thoracic lymph node lesions continued to increase. A pathological autopsy was performed with the family’s consent to investigate potential resistance mechanisms. RNA sequencing and additional analyses revealed increased VEGF-A expression in metastatic lymph node lesions, suggesting a role in sotorasib resistance. These findings provide insights into the potential molecular mechanisms underlying treatment resistance in KRAS p.G12C-mutant IMA.https://doi.org/10.1038/s41698-025-00953-2 |
| spellingShingle | Hiraku Yanada Ryohei Yoshida Ryotaro Kida Kiichi Nitanai Maya Ikeda Kazunori Nagasue Taeka Naraoka Masashi Ueda Takashi Watanabe Ryota Shigaki Yasuhiro Umekage Yoshinori Minami Toshihiro Nagato Manami Hayashi Sayaka Yuzawa Mishie Tanino Takaaki Sasaki Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-A npj Precision Oncology |
| title | Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-A |
| title_full | Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-A |
| title_fullStr | Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-A |
| title_full_unstemmed | Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-A |
| title_short | Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-A |
| title_sort | sotorasib resistance in kras g12c mutant invasive mucinous adenocarcinoma with implications for vegf a |
| url | https://doi.org/10.1038/s41698-025-00953-2 |
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