Microscaled proteogenomic methods for precision oncology
| Autor: | Cynthia X. Ma, Foluso O. Ademuyiwa, Mothaffar F. Rimawi, Meenakshi Anurag, Chen Huang, Michael A. Gillette, Terry Hyslop, Jeremy Hoog, Yongchao Dou, Alexander B. Saltzman, Eric J. Jaehnig, Rachel Schiff, Suhas Vasaikar, Mark A. Watson, Doug W. Chan, D. R. Mani, Karl R. Clauser, Bo Wen, Beom-Jun Kim, Karsten Krug, Anna Malovannaya, Ari Gao, David G. Mutch, Shankha Satpathy, Kimberly R. Holloway, Bing Zhang, Samuel Jacobs, Steven A. Carr, Matthew J. Ellis, Purba Singh, Charles M. Perou, George Miles, Noel Namai |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Receptor ErbB-2 Science General Physics and Astronomy Down-Regulation Genomics Breast Neoplasms Pilot Projects Computational biology Proteomics General Biochemistry Genetics and Molecular Biology Article Transcriptome 03 medical and health sciences 0302 clinical medicine Breast cancer Trastuzumab Humans Medicine lcsh:Science skin and connective tissue diseases neoplasms PI3K/AKT/mTOR pathway Cancer Proteogenomics Multidisciplinary business.industry TOR Serine-Threonine Kinases Biological techniques Mucin General Chemistry medicine.disease 3. Good health Clinical trial Androgen receptor 030104 developmental biology 030220 oncology & carcinogenesis Cancer research lcsh:Q Biopsy Large-Core Needle business Signal Transduction medicine.drug |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a proteogenomics approach for core biopsies using tissue-sparing specimen processing and microscaled proteomics. As a demonstration, we analyze core needle biopsies from ERBB2 positive breast cancers before and 48–72 h after initiating neoadjuvant trastuzumab-based chemotherapy. We show greater suppression of ERBB2 protein and both ERBB2 and mTOR target phosphosite levels in cases associated with pathological complete response, and identify potential causes of treatment resistance including the absence of ERBB2 amplification, insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification, and candidate resistance mechanisms including androgen receptor signaling, mucin overexpression and an inactive immune microenvironment. The clinical utility and discovery potential of proteogenomics at biopsy-scale warrants further investigation. Connecting genomics and proteomics allows the development of more efficient and specific treatments for cancer. Here, the authors develop proteogenomic methods to defining cancer signaling in-vivo starting from core needle biopsies and with application to a HER2 breast cancer focused clinical trial. |
| Databáze: | OpenAIRE |
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