In the literature: October 2019

Autor: Andrés Cervantes, Paolma Martín-Martorell, Noelia Tarazona, Valentina Gambardella
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: ESMO Open
ESMO Open, Vol 4, Iss 6 (2019)
ISSN: 2059-7029
Popis: Gastrointestinal cancers are a subset of molecularly heterogeneous diseases. In the era of personalised medicine, major efforts are being made towards stratifying patients according to molecular profiling. However, although most treatments are currently based on targeted therapy in relation to specific genomic alterations, acquired resistance emerges during anticancer therapies and subsequently treatment failure occurs. Intratumour heterogeneity plays a significant role in the acquisition of resistance by clonal evolution of tumour cell populations under therapeutic pressure. Despite a single tumour biopsy represents the standard for cancer research and drives our therapeutic decisions, limitations in terms of acquisition and utility, and underestimation of the genomic landscape of tumours are found. Analysis of circulating tumour DNA (ctDNA) overcomes these barriers and allows us a more comprehensive study of tumour capturing intratumour heterogeneity to identify resistance to targeted therapy to better select subsequent treatment. Parikh et al 1 recently published in Nature Medicine an article that demonstrates how a single tissue biopsy fails to identify multiple acquired resistance mechanisms compared with ctDNA analysis across different gastrointestinal cancers. This study is the largest comparing ctDNA to tumour biopsy characterisation after disease progression to tailored therapy. ctDNA post-progression from 42 patients diagnosed with different gastrointestinal cancers was analysed by next-generation sequencing (NGS) and/or whole-exome sequencing identifying at least one resistance mechanisms in 32 of 42 (76%) patients and multiple resistance alterations in 17 of 32 (53%) individuals. In contrast, tumour biopsy identified a resistance alteration in 11 of 23 (48%) cases and multiples mechanisms in only 2 of the 23 (9%) patients with tumour tissue available at this time. Interestingly, it was possible to analyse tumour tissue from different regions or metastasis in five patients demonstrating distinct resistance alterations depending on the biopsy site. ctDNA analysis detected all resistance mechanisms identified in the different metastatic lesions …
Databáze: OpenAIRE
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