Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion

Chu, Quincy S.

doi:10.1177/1758835919895756

Cited by 49 publications

(33 citation statements)

References 223 publications

(318 reference statements)

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“…Lung cancer has been one of the most deadly cancer for decades worldwide. However, the present treatment strategy is imperfect, especially in non-driver-mutation-type lung cancer [ 30 ]. In this study, advanced techniques, NGS and bioinformatics were utilized to discover and validate LSAMP in lung cancer tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

The Downregulation of LSAMP Expression Promotes Lung Cancer Progression and Is Associated with Poor Survival Prognosis

Chang

et al. 2021

JPM

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Lung cancer has been a leading cause of cancer-related death for decades and therapeutic strategies for non-driver mutation lung cancer are still lacking. A novel approach for this type of lung cancer is an emergent requirement. Here we find that loss of LSAMP (Limbic System Associated Membrane Protein), compared to other IgLON family of proteins NTM (Neurotrimin) and OPCML (OPioid-binding Cell adhesion MoLecule), exhibits the strongest prognostic and therapeutic significance in predicting lung adenocarcinoma (LUAD) progression. Lower expression of LSAMP and NTM, but not OPCML, were found in tumor parts compared with normal parts in six LUAD patients, and this was validated by public datasets, Oncomine® and TCGA. The lower expression of LSAMP, but not NTM, was correlated to shorter overall survival. Two epigenetic regulations, including hypermethylation and miR-143-3p upregulation but not copy number variation, were associated with downregulation of LSAMP in LUAD patients. Pathway network analysis showed that NEGR1 (Neuronal Growth Regulator 1) was involved in the regulatory loop of LSAMP. The biologic functions by LSMAP knockdown in lung cancer cells revealed LSMAP was linked to cancer cell migration via epithelial-mesenchymal transition (EMT) but not proliferation nor stemness of LUAD. Our result showed for the first time that LSAMP acts as a potential tumor suppressor in regulating lung cancer. A further deep investigation into the role of LSAMP in lung cancer tumorigenesis would provide therapeutic hope for such affected patients.

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Section: Discussionmentioning

confidence: 99%

The Downregulation of LSAMP Expression Promotes Lung Cancer Progression and Is Associated with Poor Survival Prognosis

Chang

et al. 2021

JPM

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“…For EGFR activating mutation-positive tumours or ALK/ROS1 fusion-positive tumours, the high response rate (43–80% for EGFR tyrosine kinase inhibitor {TKIs} [ 67 , 68 , 69 , 70 , 71 ] and 60–92% for ALK TKIs [ 72 , 73 , 74 , 75 , 76 ]), increased survival, and excellent tolerability of oral TKIs make these the agents of choice [ 77 ]. When a tumour is found to harbour a driver mutation as well as being PD-L1 high, treatment with the appropriate TKI is recommended [ 66 ].…”

Section: Non-small Cell Lung Cancermentioning

confidence: 99%

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults

et al. 2021

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The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. These NTRK gene fusions are oncogenic drivers found in most tumour types at a low frequency (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., secretory carcinoma of the salivary gland and of the breast). They are generally mutually exclusive of other common oncogenic drivers. Larotrectinib and entrectinib have demonstrated impressive overall response rates and tolerability in Phase I/II trials in patients with TRK fusion cancer with no other effective treatment options. Given the low frequency of TRK fusion cancer and the heterogeneous molecular testing landscape in Canada, identifying and optimally managing such patients represents a new challenge. We provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor. We focus on five tumour types: thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, soft tissue sarcoma, and salivary gland carcinoma. Based on the probability of the tumour harbouring an NTRK gene fusion, we also suggest a tumour-agnostic consensus for NTRK gene fusion testing and treatment. We recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options.

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“…Currently, first‐generation EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs, [gefitinib, erlotinib, and icotinib]) and second‐generation EGFR‐TKI (afatinib)‐targeted therapy have demonstrated improved efficacy over conventional chemotherapy for advanced EGFR‐mutant patients and is generally accepted as the standard first‐line treatment, followed by sequential chemotherapy or third‐generation EGFR‐TKIs with EGFR T790 M mutation after disease progression 6‐8 . However, the median progression‐free survival (PFS) for first‐generation EGFR‐TKIs was less than a year 9 .…”

Section: Introductionmentioning

confidence: 99%

Cost‐effectiveness analysis of first‐line treatments for advanced epidermal growth factor receptor‐mutant non‐small cell lung cancer patients

Chai

et al. 2021

Cancer Medicine

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Objectives Recent studies showed prolonged survival for advanced epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) patients treated with both monotherapies and combined therapies. However, high costs limit clinical applications. Thus, we conducted this cost‐effectiveness analysis to explore an optimal first‐line treatment for advanced EGFR‐mutant NSCLC patients. Materials and Methods Survival data were extracted from six clinical trials, including ARCHER1050 (dacomitinib vs. gefitinib); FLAURA (osimertinib vs. gefitinib/erlotinib); JO25567 and NEJ026 (bevacizumab +erlotinib vs. erlotinib); NEJ009 (gefitinib +chemotherapy vs. gefitinib); and NCT02148380 (gefitinib +chemotherapy vs. gefitinib vs. chemotherapy) trials. Cost‐related data were obtained from hospitals and published literature. The effect parameter (quality‐adjusted life year [QALY]) was the reflection of both survival and utility. Incremental cost‐effectiveness ratio (ICER), average cost‐effectiveness ratio (ACER), and net benefit were calculated, and the willingness‐to‐pay (WTP) threshold was set at $30828/QALY from the perspective of the Chinese healthcare system. Sensitivity analysis was performed to explore the stability of results. Results We compared treatment groups with control groups in each trial. ICERs were $1897750.74/QALY (ARCHER1050), $416560.02/QALY (FLAURA), ‐$477607.48/QALY (JO25567), ‐$464326.66/QALY (NEJ026), ‐$277121.22/QALY (NEJ009), ‐$399360.94/QALY (gefitinib as comparison, NCT02148380), and ‐$170733.05/QALY (chemotherapy as comparison, NCT02148380). Moreover, ACER and net benefit showed that the combination of EGFR‐TKI with chemotherapy and osimertinib was of more economic benefit following first‐generation EGFR‐TKIs. Sensitivity analyses showed that the impact of utilities and monotherapy could be cost‐effective with a 50% cost reduction. Conclusion First‐generation EGFR‐TKI therapy remained the most cost‐effective treatment option for advanced EGFR‐mutant NSCLC patients. Our results could serve as both a reference for both clinical practice and the formulation of medical insurance reimbursement.

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Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion

Cited by 49 publications

References 223 publications

The Downregulation of LSAMP Expression Promotes Lung Cancer Progression and Is Associated with Poor Survival Prognosis

The Downregulation of LSAMP Expression Promotes Lung Cancer Progression and Is Associated with Poor Survival Prognosis

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults

Cost‐effectiveness analysis of first‐line treatments for advanced epidermal growth factor receptor‐mutant non‐small cell lung cancer patients

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