| Literature DB >> 29990497 |
Giulia Siravegna1, Luca Lazzari2, Giovanni Crisafulli3, Andrea Sartore-Bianchi4, Benedetta Mussolin1, Andrea Cassingena4, Cosimo Martino1, Richard B Lanman5, Rebecca J Nagy5, Stephen Fairclough5, Giuseppe Rospo1, Giorgio Corti1, Alice Bartolini1, Pamela Arcella1, Monica Montone1, Francesca Lodi6, Annalisa Lorenzato6, Alice Vanzati4, Emanuele Valtorta4, Giovanni Cappello1, Andrea Bertotti3, Sara Lonardi7, Vittorina Zagonel7, Francesco Leone3, Mariangela Russo1, Antonella Balsamo1, Mauro Truini4, Federica Di Nicolantonio3, Alessio Amatu4, Erica Bonazzina4, Silvia Ghezzi4, Daniele Regge1, Angelo Vanzulli8, Livio Trusolino3, Salvatore Siena8, Silvia Marsoni9, Alberto Bardelli10.
Abstract
Targeting HER2 is effective in 24% of ERBB2 amplified metastatic colorectal cancer; however, secondary resistance occurs in most of the cases. We studied the evolution of individual metastases during treatment to discover spatially resolved determinants of resistance. Circulating tumor DNA (ctDNA) analysis identified alterations associated with resistance in the majority of refractory patients. ctDNA profiles and lesion-specific radiographic reports revealed organ- or metastasis-private evolutionary patterns. When radiologic assessments documented progressive disease in target lesions, response to HER2 blockade was retained in other metastases. Genomic and functional analyses on samples and cell models from eight metastases of a patient co-recruited to a postmortem study unveiled lesion-specific evolutionary trees and pharmacologic vulnerabilities. Lesion size and contribution of distinct metastases to plasma ctDNA were correlated.Entities:
Keywords: HER2 amplification; clonal evolution; colorectal cancer; ctDNA; lapatinib; liquid biopsy; rapid autopsy; resistance; targeted therapy; trastuzumab
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Year: 2018 PMID： 29990497 DOI： 10.1016/j.ccell.2018.06.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743