Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations

Joshi, Asim; Mishra, Rohit; Desai, Sanket; Chandrani, Pratik; Kore, Hitesh; Sunder, Roma; Hait, Supriya; Iyer, Prajish; Trivedi, Vaishakhi; Choughule, Anuradha; Noronha, Vanita; Joshi, Amit; Patil, Vijay; Menon, Nandini; Kumar, Rajiv; Prabhash, Kumar; Dutt, Amit

doi:10.18632/oncotarget.27905

Cited by 14 publications

(9 citation statements)

References 51 publications

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“…Epidermal growth factor receptor (EGFR) represents as the most frequently mutated driver gene in lung cancer. In comparison with lung adenocarcinoma, EGFR mutations are relatively rare lung squamous cell carcinoma (SCC), with a reported prevalence of 3% to 18% (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). In light of this, the therapeutic value of targeted therapy, EGFR tyrosine kinase inhibitors (EGFR-TKIs), in advanced lung SCC patients lacks in-depth multiple dimensional exploration with large cohorts.…”

Section: Introductionmentioning

confidence: 99%

EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes

et al. 2021

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BackgroundThe therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy.Material and MethodsWe consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI–treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed.ResultsIn total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P<0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS.ConclusionsEGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.

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Section: Introductionmentioning

confidence: 99%

EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes

et al. 2021

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“…The other major novel molecular finding is the uniquely high rate of FGFR1 amplifications in these tumours (71%). FGFR1 amplifications are most commonly encountered in LUSC (11%) and only rarely in LUAD (0.7%); 18,19 the rate is significantly exaggerated in TTF1/p40 dual‐positive tumours compared to both LUAD and LUSC. The high rate of FGFR1 amplification may offer a unique approach to therapeutic targeting of these tumours, as FGF/FGFR signalling axis inhibition by tyrosine kinase inhibitors such as erdafitinib was shown to be an effective therapy in different tumour types, including NSCLC 19–21 …”

Section: Discussionmentioning

confidence: 99%

Non‐small cell lung carcinomas with diffuse coexpression of TTF1 and p40: clinicopathological and genomic features of 14 rare biphenotypic tumours

et al. 2022

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Non-small cell lung carcinomas with diffuse coexpression of TTF1 and p40: clinicopathological and genomic features of 14 rare biphenotypic tumours poorly differentiated NSCLCs with frequent basaloid features, but some show evidence of focal squamous, glandular or dual differentiation with a distinctly high rate of FGFR1 amplifications. The presence of targetable LUAD-type alterations (EGFR, KRAS G12C) emphasizes the importance of molecular testing in these tumours.

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“…For samples tested by NGS, genomic alterations were identified using the computational best practices pipeline, WaterHose-ClinOme. [11][12][13] Those with targetable alterations were recommended suitable therapy on the basis of data available from various trials conducted globally for patients with genomic alterations while considering the availability and affordability of drugs in our setting. Considering the clinical data and molecular test reports, recommendations were made for each patient either for continuation of ongoing therapy, starting a new therapy, performing a new diagnostic test, or consideration of enrollment in a clinical trial.…”

Section: Study Detailsmentioning

confidence: 99%

Impact of Molecular Tumor Board on the Clinical Management of Patients With Cancer

Behel

Noronha

Choughule

et al. 2022

JCO Global Oncology

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PURPOSE Multidisciplinary molecular tumor boards (MTBs) help in interpreting complex genomic data generated by molecular tumor profiling and improve patients' access to targeted therapies. The purpose of this study was to assess the impact of our institution's MTB on the clinical management of patients with cancer. METHODS This study was conducted at a tertiary cancer center in India. Cases to be discussed in the MTB were identified by molecular pathologists, scientists, or oncologists. On the basis of the clinical data and molecular test reports, a course of clinical management was recommended and made available to the treating oncologist. We determined the proportion of patients who were recommended a change in the clinical management. We also assessed compliance of the treating oncologists with MTB recommendations. RESULTS There were 339 discussions for 328 unique patients. The median age of the cohort was 54 years (range 17-87), and the majority of the patients were men (65.1%). Of 339 cases, 133 (39.2%) were recommended continuation of ongoing therapy while the remaining 206 (60.7%) were recommended a change in clinical management. Compliance with MTB recommendations for a change in clinical management was 58.5% (79 of 138 evaluable cases). Compliance and implementation for MTB's recommendation to start a new therapy in 104 evaluable cases were 60.5% and 44.2%, respectively. A total of 248 biopsies had at least one actionable mutation. A total of 646 mutations were identified in the cohort, with EGFR being the most frequently altered gene. CONCLUSION MTBs help in interpreting results of molecular tests, understanding the significance of molecular abnormalities, and assessing the benefits of available targeted therapies and clinical trials in the management of patients with targetable genetic alterations.

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Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations

Cited by 14 publications

References 51 publications

EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes

EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes

Non‐small cell lung carcinomas with diffuse coexpression of TTF1 and p40: clinicopathological and genomic features of 14 rare biphenotypic tumours

Impact of Molecular Tumor Board on the Clinical Management of Patients With Cancer

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