Reliability of panel-based mutational signatures for immune-checkpoint-inhibition efficacy prediction in non-small cell lung cancer

Article Oncology

Tobacco Smoking-Related Mutational Signatures in Classifying Smoking-Associated and Nonsmoking-Associated NSCLC

Sophie M. Ernst et al.

Summary: Next-generation sequencing allows for the reclassification of smoking-associated NSCLC based on individual genomic tumor characteristics, which can help reduce lung cancer stigma.

JOURNAL OF THORACIC ONCOLOGY (2023)

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Article Genetics & Heredity

Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer

Arvind Ravi et al.

Summary: Genomic and transcriptomic analysis of 393 non-small cell lung cancer patients treated with checkpoint inhibitors reveals molecular features associated with treatment response. The study analyzes data from the Stand Up To Cancer-Mark Foundation cohort, including whole exome and/or RNA sequencing, and identifies associations between molecular features and outcome, such as genomic subgroups, expression of immunoproteasome components, and tumor-intrinsic subtype. The findings demonstrate the complexity of immunotherapy outcomes and highlight the discovery potential of integrative analysis in well-curated cancer-specific cohorts.

NATURE GENETICS (2023)

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Article Multidisciplinary Sciences

Using genomic scars to select immunotherapy beneficiaries in advanced non-small cell lung cancer

H. C. Donker et al.

Summary: By analyzing DNA mutations in pre-treatment tissue, researchers have identified specific mutational signatures that are associated with response to immunotherapy in advanced non-small cell lung cancer patients. This finding could potentially help select patients who are likely to benefit from immunotherapy.

SCIENTIFIC REPORTS (2023)

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Article Pathology

Biomarkers of response to checkpoint inhibitors beyond PD-L1 in lung cancer

Lynette M. Sholl

Summary: Immunotherapy is crucial in the management of non-small cell lung carcinoma, but responses vary widely. PD-L1 protein expression serves as a predictive biomarker, yet its sensitivity and specificity are suboptimal. Insights into tumor and host immune-specific factors are defining better immunotherapy biomarkers beyond immune checkpoint expression status.

MODERN PATHOLOGY (2022)

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Article Pathology

Evaluation of the TruSight Oncology 500 Assay for Routine Clinical Testing of Tumor Mutational Burden and Clinical Utility for Predicting Response to Pembrolizumab

Bo Wei et al.

Summary: This study evaluated the clinical utility of TSO500, a gene testing method, for determining the eligibility of patients for pembrolizumab treatment. The results showed a high concordance between TSO500 and two reference methods, indicating that TSO500 can effectively predict the response to pembrolizumab in patients with high TMB levels.

JOURNAL OF MOLECULAR DIAGNOSTICS (2022)

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Article Oncology

HLA-I diversity and tumor mutational burden by comprehensive next-generation sequencing as predictive biomarkers for the treatment of non-small cell lung cancer with PD-(L)1 inhibitors

Kristof Cuppens et al.

Summary: In this study, comprehensive next-generation sequencing revealed that HLA-I diversity can predict durable clinical benefit in non-small cell lung cancer patients treated with immune checkpoint inhibitors, while TMB was confirmed as a predictive biomarker.

LUNG CANCER (2022)

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Review Genetics & Heredity

Therapeutic and prognostic insights from the analysis of cancer mutational signatures

Samuel W. Brady et al.

Summary: Somatic mutations in cancer genomes are caused by multiple mutational processes, each leaving a characteristic imprint. Decoding these imprints can provide insights into the evolutionary history of tumors. Mutational signatures can also offer therapeutic and prognostic insights, acting as biomarkers for drug response and prognosis. Additionally, therapy-induced mutational signatures have been associated with cancer progression.

TRENDS IN GENETICS (2022)

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Article Medicine, Research & Experimental

Association of clock-like mutational signature with immune checkpoint inhibitor outcome in patients with melanoma and NSCLC

Wei Chong et al.

Summary: This study investigated the association between tumor genomic features and clinical benefit of ICI treatment, revealing that an age-related clock-like mutational signature is linked to worse prognosis and lower immune activity. The findings suggest opportunities to stratify patients into optimal immunotherapy plans based on genomic subtyping.

MOLECULAR THERAPY-NUCLEIC ACIDS (2021)

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Article Respiratory System

Mutational signature analysis in non-small cell lung cancer patients with a high tumor mutational burden

Guus R. M. van den Heuvel et al.

Summary: This study investigated mutational signatures in NSCLC patients using tumor DNA samples, revealing a prominent presence of SBS4 signature in tumors associated with smoking, and SBS2 and/or SBS13 signatures linked to AID/APOBEC enzyme activity. SBS4 signature was significantly more present in early stages of NSCLC, indicating potential clinical significance. Further studies are needed to determine the clinical utility of mutational signature analyses.

RESPIRATORY RESEARCH (2021)

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Article Hematology