Cargando…
Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences
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 patien...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130298/ https://www.ncbi.nlm.nih.gov/pubmed/35610322 http://dx.doi.org/10.1038/s41598-022-12669-5 |
_version_ | 1784712957961175040 |
---|---|
author | Yao, Shuyang Meric-Bernstam, Funda Hong, David Janku, Filip Naing, Aung Piha-Paul, Sarina Anne Tsimberidou, Apostolia Maria Karp, Daniel Subbiah, Vivek Yap, Timothy Anthony Ahnert, Jordi Rodon Pant, Shubham Dumbrava, Ecaterina E Ileana Wathoo, Chetna Campbell, Erick Yu, Lihou Yamamura, Yuko Fu, Siqing |
author_facet | Yao, Shuyang Meric-Bernstam, Funda Hong, David Janku, Filip Naing, Aung Piha-Paul, Sarina Anne Tsimberidou, Apostolia Maria Karp, Daniel Subbiah, Vivek Yap, Timothy Anthony Ahnert, Jordi Rodon Pant, Shubham Dumbrava, Ecaterina E Ileana Wathoo, Chetna Campbell, Erick Yu, Lihou Yamamura, Yuko Fu, Siqing |
author_sort | Yao, Shuyang |
collection | PubMed |
description | 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/m(2), 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. |
format | Online Article Text |
id | pubmed-9130298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91302982022-05-26 Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences Yao, Shuyang Meric-Bernstam, Funda Hong, David Janku, Filip Naing, Aung Piha-Paul, Sarina Anne Tsimberidou, Apostolia Maria Karp, Daniel Subbiah, Vivek Yap, Timothy Anthony Ahnert, Jordi Rodon Pant, Shubham Dumbrava, Ecaterina E Ileana Wathoo, Chetna Campbell, Erick Yu, Lihou Yamamura, Yuko Fu, Siqing Sci Rep Article 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/m(2), 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. Nature Publishing Group UK 2022-05-24 /pmc/articles/PMC9130298/ /pubmed/35610322 http://dx.doi.org/10.1038/s41598-022-12669-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yao, Shuyang Meric-Bernstam, Funda Hong, David Janku, Filip Naing, Aung Piha-Paul, Sarina Anne Tsimberidou, Apostolia Maria Karp, Daniel Subbiah, Vivek Yap, Timothy Anthony Ahnert, Jordi Rodon Pant, Shubham Dumbrava, Ecaterina E Ileana Wathoo, Chetna Campbell, Erick Yu, Lihou Yamamura, Yuko Fu, Siqing Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences |
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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130298/ https://www.ncbi.nlm.nih.gov/pubmed/35610322 http://dx.doi.org/10.1038/s41598-022-12669-5 |
work_keys_str_mv | AT yaoshuyang clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT mericbernstamfunda clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT hongdavid clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT jankufilip clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT naingaung clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT pihapaulsarinaanne clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT tsimberidouapostoliamaria clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT karpdaniel clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT subbiahvivek clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT yaptimothyanthony clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT ahnertjordirodon clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT pantshubham clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT dumbravaecaterinaeileana clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT wathoochetna clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT campbellerick clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT yulihou clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT yamamurayuko clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences AT fusiqing clinicalcharacteristicsandoutcomesofphaseicancerpatientswithccne1amplificationmdandersonexperiences |