Description of the genetic variants identified in a cohort of patients diagnosed with localized anal squamous cell carcinoma and treated with panitumumab
Trilla-Fuertes, Lucía (Biomedica Molecular Medicine (Madrid))
Gámez-Pozo, Angelo (Instituto de Investigación Sanitaria del Hospital Universitario La Paz)
Maurel, Joan (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
García-Carbonero, Rocío (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Capdevila Castillón, Jaume (Vall d'Hebron Institut d'Oncologia)
G-Pastrián, Laura (Hospital Universitario La Paz (Madrid))
Mendiola, Marta (Centro de Investigación Biomédica en Red de Cáncer)
Peña, Cristina (Hospital Universitario La Paz (Madrid))
López-Vacas, Rocío (Instituto de Investigación Sanitaria del Hospital Universitario La Paz)
Cuatrecasas, Miriam (Hospital Clínic i Provincial de Barcelona)
García-Alfonso, Pilar (Hospital General Universitario Gregorio Marañón)
Ramos-Ruiz, Ricardo (Genomics Unit Cantoblanco)
Llorens, Carlos (Biotechvana SL (Madrid))
Ghanem, Ismael (Hospital Universitario La Paz (Madrid))
Conill, Carles (Hospital Clínic i Provincial de Barcelona)
Heredia Soto, Victoria (Instituto de Investigación Sanitaria del Hospital Universitario La Paz)
Campos-Barros, Ángel (Instituto de Investigación Sanitaria del Hospital Universitario La Paz)
Fresno Vara, Juan Ángel (Centro de Investigación Biomédica en Red de Cáncer)
Feliu, Jaime (Universidad Autónoma de Madrid)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	Squamous cell carcinoma is the most frequent histologic type of anal carcinoma. The standard of care since the 1970s has been a combination of 5-fluorouracil, mitomycin C, and radiotherapy. This treatment is very effective in T1/T2 tumors (achieving complete regression in 80-90% of tumors). However, in T3/T4 tumors, the 3-year relapse free survival rate is only 50%. The VITAL trial aimed to assess the efficacy and safety of panitumumab in combination with this standard treatment. In this study, 27 paraffin-embedded samples from the VITAL trial and 18 samples from patients from daily clinical practice were analyzed by whole-exome sequencing and the influence of the presence of genetic variants in the response to panitumumab was studied. Having a moderate- or high-impact genetic variant in PIK3CA seemed to be related to the response to panitumumab. Furthermore, copy number variants in FGFR3, GRB2 and JAK1 were also related to the response to panitumumab. These genetic alterations have also been studied in the cohort of patients from daily clinical practice (not treated with panitumumab) and they did not have a predictive value. Therefore, in this study, a collection of genetic alterations related to the response with panitumumab was described. These results could be useful for patient stratification in new anti-EGFR clinical trials.
Ajuts:	Ministerio de Economía y Competitividad DI-15-07614
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cancer ; Medical genetics ; Predictive markers
Publicat a:	Scientific reports, Vol. 11 (april 2021) , ISSN 2045-2322

DOI: 10.1038/s41598-021-86966-w
PMID: 33795829

9 p, 1.6 MB

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