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Background: Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing-based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible.
Methods: To investigate the association between a patient's responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients.
Results: We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type-specific mutation signature for chemotherapy selection.
Conclusion: Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.
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http://dx.doi.org/10.1186/s12890-024-03124-4 | DOI Listing |
J Mol Diagn
June 2025
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York. Electronic address:
Oncogenic fusion detection is an essential part of clinical diagnosis and management of non-small-cell lung carcinoma. Numerous methods are available for detection of oncogenic fusions in the clinical laboratory, although RNA sequencing has rapidly gained prominence. Accordingly, however, multiple different RNA-sequencing assays exist, with diverse methods and varying performance characteristics.
View Article and Find Full Text PDFESMO Open
April 2025
Department of Genetics, University of Delhi South Campus, New Delhi, India. Electronic address:
Background: Lung adenocarcinoma frequently presents with EGFR mutations, often progressing on EGFR tyrosine kinase inhibitors (TKIs) despite an initial response. Progression is frequently driven by additional genetic changes, including mutations in tumor suppressor genes (TSGs). Understanding the role of these concurrent TSG mutations can help elucidate resistance mechanisms and guide the development of more effective treatment approaches.
View Article and Find Full Text PDFLung Cancer (Auckl)
February 2025
Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA, USA.
Background: mutations are generally divided into three classes based on the different altered mechanism of activation.
Methods: We queried the public AACR GENIE database (version 13.1), which includes tumor mutation burden (TMB) data, to explore potential molecular differences among the three classes of non-small cell lung cancer (NSCLC).
Cancer Med
February 2025
Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, California, USA.
Background: Receptor tyrosine kinase (RTK) inhibitors have been approved for the treatment of NTRK fusion (NTRK+) and RET fusion (RET+) positive solid tumors in a tumor-agnostic manner. However, the objective response rate was the lowest among entrectinib-treated NTRK+ colorectal cancer (CRC) (20%) and selpercatinib-treated RET+ CRC (20%) among all NTRK+, and RET+ solid tumors, respectively.
Methods: We compared tumor mutation burden (TMB) in NTRK+/RET+ CRC with all other NTRK+ and RET+ solid tumors using the American Association for Cancer Research (AACR) GENIE database (Version 13.
J Natl Cancer Inst
January 2025
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Background: Alterations in forkhead box A1 (FOXA1), a pioneer transcription factor, are associated with poor prognosis in breast cancer and prostate cancer. We characterized FOXA1 genomic alterations and their clinical impacts in a large pan-cancer cohort from the American Association for Cancer Research Genomics, Evidence, Neoplasia, Information, Exchange database.
Methods: FOXA1 alterations were characterized across more than 87 000 samples from more than 30 cancer types for primary and metastatic tumors alongside patient characteristics and clinical outcomes.