Measuring tumor mutation burden in non-small cell lung cancer: Tissue versus liquid biopsy
Open accessAbstract
The introduction in the clinic of immune checkpoint inhibitors (IOs) has represented an important improvement for the treatment of patients with advanced non-small cell lung cancer (NSCLC). These drugs have shown a higher activity as compared with chemotherapy in both first- and second-line of treatment, with some patients experiencing a long-lasting response. More recently, combinations of IOs have entered clinical trials in different tumor types including NSCLC. Nevertheless, IOs are active only in a subgroup of patients and biomarkers for appropriate patients' selection are urgently needed to offer the patients an effective therapy, and also to manage the costs. Tumor mutation burden (TMB) has powerfully emerged as a potential biomarker for immunotherapy and might enter the clinic in the next months, although different challenges are still unsolved. Different methods exist to evaluate TMB in tissue, ranging from whole exome sequencing (WES) to targeted sequencing of smaller sets of genes, which need to be fully standardized to ensure that patients receive an appropriate TMB test with clear clinical interpretation. In addition, as already happened for the implementation of liquid biopsy testing from NSCLC patients to identify targetable alterations, researchers are also evaluating the possibility to calculate TMB in blood, to further enlarge the number of NSCLC patients who may benefit from immunotherapy. Preliminary data highlight the difficulty to develop targeted sequencing panels for the assessment of TMB starting from the circulating cell free DNA (cfDNA). The applicability of TMB testing on liquid biopsy needs further investigation and may be clarified within the ongoing clinical trials.
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Combination therapy with ICIs plus other therapeutic approaches such as chemotherapy, radiotherapy, cancer vaccines, and CXCR4 blockade therapy can efficiently circumvent tumour resistance to ICI therapy.
“Accordingly, several studies have exhibited that combination therapy with ICIs plus other therapeutic approaches, such as chemotherapy [86], radiotherapy, cancer vaccines, and also CXCR4 blockade therapy [87] can efficiently circumvent tumour resistance to ICI therapy.”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [87]
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- © Translational lung cancer research. All rights reserved. Transl Lung Cancer Res 2018;7(6):668-677 tlcr.amegroups.com
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Immune Checkpoint Inhibitors in Cancer Therapy
Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353 · see citing works
- Authors
- Fenizia, F., Pasquale, R., Roma, C., Bergantino, F., Iannaccone, A., & Normanno, N.
- Affiliations
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Venue
- Translational Lung Cancer Research
- Publisher
- AME Publishing Company
- Published
- 2018-12
- Volume
- 7
- Issue
- 5
- Pages
- 668-677
- ISSN
- 2218-6751 (ISSN-L)
- 2226-4477
- PMC
- PMC6249618
- OpenAlex
- W2898076764
- Cited by
- 69
- References
- 46
- Citations by year
- 2026: 5 · 2024: 4 · 2023: 4 · 2022: 12 · 2021: 18 · 2020: 17 · 2019: 8 · 2013: 1
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Translational Lung Cancer Research (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- tumor mutational burden, non-small cell lung cancer, liquid biopsy, cell-free DNA, tissue biopsy, immune checkpoint inhibitors, immunotherapy biomarkers, gene panel, exome sequencing, patient selection
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