Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences
Abstract Cyclin E is frequently encoded by CCNE1 gene amplification in various malignancies. We reviewed the medical records of patients with solid tumors displaying CCNE1 amplification to determine the effect of this amplification for future therapeutic development. We reviewed the medical records...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-12669-5 |
| _version_ | 1828222354236375040 |
|---|---|
| author | Shuyang Yao Funda Meric-Bernstam David Hong Filip Janku Aung Naing Sarina Anne Piha-Paul Apostolia Maria Tsimberidou Daniel Karp Vivek Subbiah Timothy Anthony Yap Jordi Rodon Ahnert Shubham Pant Ecaterina E Ileana Dumbrava Chetna Wathoo Erick Campbell Lihou Yu Yuko Yamamura Siqing Fu |
| author_facet | Shuyang Yao Funda Meric-Bernstam David Hong Filip Janku Aung Naing Sarina Anne Piha-Paul Apostolia Maria Tsimberidou Daniel Karp Vivek Subbiah Timothy Anthony Yap Jordi Rodon Ahnert Shubham Pant Ecaterina E Ileana Dumbrava Chetna Wathoo Erick Campbell Lihou Yu Yuko Yamamura Siqing Fu |
| author_sort | Shuyang Yao |
| collection | DOAJ |
| description | Abstract Cyclin E is frequently encoded by CCNE1 gene amplification in various malignancies. We reviewed the medical records of patients with solid tumors displaying CCNE1 amplification to determine the effect of this amplification for future therapeutic development. We reviewed the medical records of patients with advanced solid tumors harboring CCNE1 amplification who were seen at the phase I clinic between September 1, 2012, and December 31, 2019. Among 79 patients with solid tumors harboring CCNE1 amplification, 56 (71%) received phase 1 clinical trial therapy, 39 (49%) had 3 or more concurrent genomic aberrances, and 52 (66%) had a concurrent TP53 mutation. The median overall survival (OS) after patients’ initial phase I visit was 8.9 months and after their initial metastasis diagnosis was 41.4 months. We identified four factors associated with poor risk: age < 45 years, body mass index ≥ 25 kg/m2, presence of the TP53 mutation, and elevated LDH > upper limit of normal. In patients treated with gene aberration-related therapy, anti-angiogenic therapy led to significantly longer OS after their initial phase I trial therapy than those who did not: 26 months versus 7.4 months, respectively (P = 0.04). This study provided preliminary evidence that CCNE1 amplification was associated with frequent TP53 mutation and aggressive clinical outcomes. Survival benefit was observed in patients who received antiangiogenic therapy and gene aberration-related treatment, supporting the future development of a personalized approach to combine gene aberration-related therapy with antiangiogenesis for the treatment of advanced malignancies harboring CCNE1 amplification. |
| first_indexed | 2024-04-12T16:52:59Z |
| format | Article |
| id | doaj.art-a5b386ae4dfe4117b0a471663d796ae6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T16:52:59Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a5b386ae4dfe4117b0a471663d796ae62022-12-22T03:24:19ZengNature PortfolioScientific Reports2045-23222022-05-011211910.1038/s41598-022-12669-5Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiencesShuyang Yao0Funda Meric-Bernstam1David Hong2Filip Janku3Aung Naing4Sarina Anne Piha-Paul5Apostolia Maria Tsimberidou6Daniel Karp7Vivek Subbiah8Timothy Anthony Yap9Jordi Rodon Ahnert10Shubham Pant11Ecaterina E Ileana Dumbrava12Chetna Wathoo13Erick Campbell14Lihou Yu15Yuko Yamamura16Siqing Fu17Department of Thoracic Surgery, Xuanwu Hospital Capital Medical UniversityDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterInstitute of Personalized Cancer Therapy, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterDepartment of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer CenterAbstract Cyclin E is frequently encoded by CCNE1 gene amplification in various malignancies. We reviewed the medical records of patients with solid tumors displaying CCNE1 amplification to determine the effect of this amplification for future therapeutic development. We reviewed the medical records of patients with advanced solid tumors harboring CCNE1 amplification who were seen at the phase I clinic between September 1, 2012, and December 31, 2019. Among 79 patients with solid tumors harboring CCNE1 amplification, 56 (71%) received phase 1 clinical trial therapy, 39 (49%) had 3 or more concurrent genomic aberrances, and 52 (66%) had a concurrent TP53 mutation. The median overall survival (OS) after patients’ initial phase I visit was 8.9 months and after their initial metastasis diagnosis was 41.4 months. We identified four factors associated with poor risk: age < 45 years, body mass index ≥ 25 kg/m2, presence of the TP53 mutation, and elevated LDH > upper limit of normal. In patients treated with gene aberration-related therapy, anti-angiogenic therapy led to significantly longer OS after their initial phase I trial therapy than those who did not: 26 months versus 7.4 months, respectively (P = 0.04). This study provided preliminary evidence that CCNE1 amplification was associated with frequent TP53 mutation and aggressive clinical outcomes. Survival benefit was observed in patients who received antiangiogenic therapy and gene aberration-related treatment, supporting the future development of a personalized approach to combine gene aberration-related therapy with antiangiogenesis for the treatment of advanced malignancies harboring CCNE1 amplification.https://doi.org/10.1038/s41598-022-12669-5 |
| spellingShingle | Shuyang Yao Funda Meric-Bernstam David Hong Filip Janku Aung Naing Sarina Anne Piha-Paul Apostolia Maria Tsimberidou Daniel Karp Vivek Subbiah Timothy Anthony Yap Jordi Rodon Ahnert Shubham Pant Ecaterina E Ileana Dumbrava Chetna Wathoo Erick Campbell Lihou Yu Yuko Yamamura Siqing Fu Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences Scientific Reports |
| title | Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences |
| title_full | Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences |
| title_fullStr | Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences |
| title_full_unstemmed | Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences |
| title_short | Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences |
| title_sort | clinical characteristics and outcomes of phase i cancer patients with ccne1 amplification md anderson experiences |
| url | https://doi.org/10.1038/s41598-022-12669-5 |
| work_keys_str_mv | AT shuyangyao clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT fundamericbernstam clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT davidhong clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT filipjanku clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT aungnaing clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT sarinaannepihapaul clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT apostoliamariatsimberidou clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT danielkarp clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT viveksubbiah clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT timothyanthonyyap clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT jordirodonahnert clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT shubhampant clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT ecaterinaeileanadumbrava clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT chetnawathoo clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT erickcampbell clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT lihouyu clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT yukoyamamura clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT siqingfu clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences |