Tumour mutational burden: clinical utility, challenges and emerging improvements.
Details
Serval ID
serval:BIB_9751CA3C1CED
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tumour mutational burden: clinical utility, challenges and emerging improvements.
Journal
Nature reviews. Clinical oncology
ISSN
1759-4782 (Electronic)
ISSN-L
1759-4774
Publication state
Published
Issued date
10/2024
Peer-reviewed
Oui
Volume
21
Number
10
Pages
725-742
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Publication Status: ppublish
Abstract
Tumour mutational burden (TMB), defined as the total number of somatic non-synonymous mutations present within the cancer genome, varies across and within cancer types. A first wave of retrospective and prospective research identified TMB as a predictive biomarker of response to immune-checkpoint inhibitors and culminated in the disease-agnostic approval of pembrolizumab for patients with TMB-high tumours based on data from the Keynote-158 trial. Although the applicability of outcomes from this trial to all cancer types and the optimal thresholds for TMB are yet to be ascertained, research into TMB is advancing along three principal avenues: enhancement of TMB assessments through rigorous quality control measures within the laboratory process, including the mitigation of confounding factors such as limited panel scope and low tumour purity; refinement of the traditional TMB framework through the incorporation of innovative concepts such as clonal, persistent or HLA-corrected TMB, tumour neoantigen load and mutational signatures; and integration of TMB with established and emerging biomarkers such as PD-L1 expression, microsatellite instability, immune gene expression profiles and the tumour immune contexture. Given its pivotal functions in both the pathogenesis of cancer and the ability of the immune system to recognize tumours, a profound comprehension of the foundational principles and the continued evolution of TMB are of paramount relevance for the field of oncology.
Keywords
Humans, Neoplasms/genetics, Neoplasms/drug therapy, Mutation, Biomarkers, Tumor/genetics, Immune Checkpoint Inhibitors/therapeutic use
Pubmed
Web of science
Create date
30/08/2024 16:48
Last modification date
01/10/2024 7:07