Abstract LB-227: Truncal activating MAPK and PI3K pathway alterations and exceptional response to dual pathway inhibition in anaplastic thyroid cancer
| العنوان: | Abstract LB-227: Truncal activating MAPK and PI3K pathway alterations and exceptional response to dual pathway inhibition in anaplastic thyroid cancer |
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| المؤلفون: | Scott L. Carter, Amaro Taylor-Weiner, Justine A. Barletta, Travis I. Zack, Levi A. Garraway, Glenn J. Hanna, Vera A. Paulson, Jochen H. Lorch, Jeremiah Wala, Francis D. Moore, Rameen Beroukhim, Antonio Calles, Thomas H. Lee, Matthew A. Nehs, William J. Gibson, Stefan Kraft, Tom Thomas, Eliezer M. Van Allen, Pasi Jäne, Fiona M. Fennessy, Daniel T. Ruan, Erik K. Alexander |
| المصدر: | Cancer Research. 76:LB-227 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Cancer Research, Pathology, medicine.medical_specialty, business.industry, Exceptional Response, medicine.disease, Blockade, Oncology, Genotype, Cancer research, Medicine, Anaplastic thyroid cancer, business, Protein kinase B, PI3K/AKT/mTOR pathway, Exome sequencing |
| الوصف: | Background: Anaplastic thyroid carcinoma (ATC) is among the most aggressive solid tumors, with a uniformly fatal prognosis. No effective systemic therapies exist. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR or combined RAF/MEK inhibition, but experienced a dramatic response when both drug regimens were combined. Methods and Results: Nine biopsies of the tumor were obtained between diagnosis and autopsy. Multi-region whole-exome sequencing revealed truncal BRAF and PIK3CA mutations, which are known to activate the MAPK and PI3K/AKT pathways respectively. We performed the largest meta-analysis of ATC to date and found a 7.4% co-occurrence of MAPK and PI3K pathway alterations in ATC. We analyzed 5,255 cancer exomes in the Cancer Genome Atlas (TCGA) to determine whether similar cancer genomes occurred outside of anaplastic thyroid carcinoma. We identified 11 tumors with BRAF V600E and non-silent PIK3CA mutations. These results indicate that this genotype occurs in other cancers and may predict response to combined therapy. Conclusions and future directions: We have identified a patient with ATC who had a dramatic response to combined inhibition of the MAPK and PI3K pathways, whereas neither MAPK inhibition nor PI3K inhibition alone was sufficient to produce tumor regression. These observations suggest that MAPK and PI3K/MTOR pathway blockade represents an effective dual therapy aimed at the founding oncogenic lesions in a subset of ATC. Citation Format: William J. Gibson, Daniel T. Ruan, Vera A. Paulson, Justine A. Barletta, Glenn J. Hanna, Stefan Kraft, Antonio Calles, Matthew Nehs, Francis Moore, Amaro Taylor-Weiner, Jeremiah Wala, Travis Zack, Thomas Lee, Fiona Fennessy, Erik Alexander, Tom Thomas, Pasi Jäne, Levi Garraway, Scott Carter, Rameen Beroukhim, Jochen Lorch, Eliezer Van Allen. Truncal activating MAPK and PI3K pathway alterations and exceptional response to dual pathway inhibition in anaplastic thyroid cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-227. |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::1b63ba065905efbae76a2de7e0fcfa2aTest https://doi.org/10.1158/1538-7445.am2016-lb-227Test |
| رقم الانضمام: | edsair.doi...........1b63ba065905efbae76a2de7e0fcfa2a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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