Clinical and technical insights of tumour mutational burden in non-small cell lung cancer

Despite the durable responses provided by the introduction of checkpoint inhibitors in advanced Non-Small Cell Lung Cancer (NSCLC) without actionable targets in a subset of patients, a large proportion of them will progress after immunotherapy. Programmed Death Ligand 1 (PD-L1) was the first biomark...

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Published in:Critical reviews in oncology/hematology 2023-02, Vol.182, p.103891-103891, Article 103891
Main Authors: Meri-Abad, Marina, Moreno-Manuel, Andrea, García, Sandra Gallach, Calabuig-Fariñas, Silvia, Pérez, Rafael Sirera, Herrero, Carlos Camps, Jantus-Lewintre, Eloisa
Format: Article
Language:English
Subjects:
B7-H1 Antigen - genetics
Biomarker
Biomarkers, Tumor - genetics
Carcinoma, Non-Small-Cell Lung - diagnosis
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - therapy
Humans
Immunotherapy
Lung Neoplasms - drug therapy
Lung Neoplasms - therapy
Mutation
NGS
NSCLC
TMB
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Summary:Despite the durable responses provided by the introduction of checkpoint inhibitors in advanced Non-Small Cell Lung Cancer (NSCLC) without actionable targets in a subset of patients, a large proportion of them will progress after immunotherapy. Programmed Death Ligand 1 (PD-L1) was the first biomarker approved for immunotherapy, although it has multiple limitations, thus the development of novel biomarkers is an urgent need. Tumour Mutational Burden (TMB) is an emerging biomarker defined as the total number of mutations per coding area of tumour genome. Targeted gene panels have emerged as a cost-effective approach to estimate TMB. However, there is still an unmet need to fully standardize sample requirements, panel size, and bioinformatic pipelines to ensure that TMB is calculated appropriately. In addition, researchers are also evaluating TMB calculation in liquid biopsy. In this work, we summarize the relevant advances and the clinical utility of TMB in NSCLC. [Display omitted] •Tumour Mutational Burden (TMB) is accurately assessed by targeted gene panels.•There is still a need for panel-based TMB harmonization and cut-off selection.•TMB is a potential useful predictive biomarker for immunotherapy in Non-Small Cell Lung Cancer.•Blood TMB has demonstrated a good correlation with tumour TMB.•More research is still needed to select the correct technological approach for blood TMB assessment.
ISSN:1040-8428
1879-0461
DOI:10.1016/j.critrevonc.2022.103891