Biological and clinical perspectives of the actionable gene fusions and amplifications involving tyrosine kinase receptors in lung cancer
Saigí, Maria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Carcereny, Enric (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Morán, Teresa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cucurull, Marc (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Domènech, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Hernández, Ainhoa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martinez-Cardús, Anna (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pros, Eva (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Sanchez-Cespedes, Montse (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Date:	2022
Abstract:	Identifying molecular oncogenic drivers is crucial for precision oncology. Genetic rearrangements, including gene fusions and gene amplification, involving and activating receptor tyrosine kinases (RTKs) are recurrent in solid tumors, particularly in non-small cell lung cancer. Advances in the tools to detect these alterations have deepened our understanding of the underlying biology and tumor characteristics and have prompted the development of novel inhibitors targeting activated RTKs. Nowadays, druggable oncogenic rearrangements are found in around 15% of lung adenocarcinomas. However, taken separately, each of these alterations has a low prevalence, which poses a challenge to their diagnosis. The identification and characterization of novel targetable oncogenic rearrangements in lung cancer continue to expand, as shown by the recent discovery of the CLIP1-LTK fusion found in 0. 4% of lung adenocarcinomas. While tyrosine kinase inhibitors that block the activity of RTKs have represented a breakthrough in the therapeutic landscape by improving the prognosis of this disease, prolonged treatment inevitably leads to the development of acquired resistance. Here, we review the oncogenic fusions and gene amplifications involving RTK in lung cancer. We address the genetic and molecular structure of oncogenic RTKs and the methods to diagnose them, emphasizing the role of next-generation sequencing technologies. Furthermore, we discuss the therapeutic implications of the different tyrosine kinase inhibitors, including the current clinical trials and the mechanisms responsible for acquired resistance. Finally, we provide an overview of the use of liquid biopsies to monitor the course of the disease.
Grants:	Instituto de Salud Carlos III JR20/00015
Note:	MS is supported by a Juan-Rodés contract from the Instituto de Salud Carlos III (JR20/00015).
Note:	This work was supported by Spanish grant from ICAPEM (ICAPEM becas 2021), to EP, and by Spanish grant form Asociación Española Contra el Cancer (AECC) (grant number GCB14142170MONT) to MSC. We thank M Rey providing language help and O Romero for data analysis support.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Lung cancer ; Gene fusions ; Gene amplification ; Tyrosine kinase receptors ; Tyrosine kinase inhibitors
Published in:	Cancer Treatment Reviews, Vol. 109 (september 2022) , p. 102430, ISSN 1532-1967

DOI: 10.1016/j.ctrv.2022.102430

12 p, 3.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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