The evolving first-line treatment of advanced non-small cell lung cancer harbouring epidermal growth factor receptor mutations

Decoster, Lore; Giron, Philippe; Mignon, S.; Grève, Jacques De

doi:10.21037/tlcr.2018.03.08

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…Accurate, reliable and timely detection of these mutations is paramount in patients with advanced NSCLC. Meaningful improvements in progression-free survival have been documented in patients harbouring EGFR mutations and ALK rearrangements [26,27,28] who have received tyrosine kinase inhibitor therapy, and case reports and case series have begun to show this may also be achievable in those patients with METex14 skipping [3,6,7,19,29,30,31,32,33].…”

Section: Discussionmentioning

confidence: 99%

Cost-Efficient and Easy to Perform PCR-Based Assay to Identify Met Exon 14 Skipping in Formalin-Fixed Paraffin-Embedded (FFPE) Non-Small Cell Lung Cancer (NSCLC) Samples

et al. 2019

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MET is a receptor tyrosine kinase (RTK) that plays important roles in carcinogenesis. Despite being frequently overexpressed in cancer, clinical responses to targeting this receptor have been limited. Recently novel splicing mutations involving the loss of exon 14 (called METex14 skipping) have emerged as potential biomarkers to predict for responsiveness to targeted therapies with Met inhibitors in non-small cell lung cancer (NSCLC). Currently, the diverse genomic alterations responsible for METex14 skipping pose a challenge for routine clinical diagnostic testing. In this report, we examine three different methodologies to detect METex14 and assess their potential utility for use as a diagnostic assay for both the identification of METex14 and intra-tumoural distribution in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Cost-Efficient and Easy to Perform PCR-Based Assay to Identify Met Exon 14 Skipping in Formalin-Fixed Paraffin-Embedded (FFPE) Non-Small Cell Lung Cancer (NSCLC) Samples

et al. 2019

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“…Despite high controversy (Caruso, 2018;Passaro and de Marinis, 2018) and earlier recommendations for use in secondline treatment (Gonzales et al, 2008;Zugazagoitia et al, 2017), dacomitinib was recently suggested as a first-line clinical therapy worldwide (Wu et al, 2017;Decoster et al, 2018;Shirley, 2018;Abdelhameed et al, 2019;Chustecka, 2019;Roeper and Griesinger, 2019). In addition, this more potent TKI could possibly find other applications such as suppressing brain tumor (Chen et al, 2019), chemoresistant ovarian cancer (Momeny et al, 2017), and breast cancer (Kalous et al, 2012) in future.…”

Section: Introductionmentioning

confidence: 99%

Deducing the Conformational Properties of a Tyrosine Kinase Inhibitor in Solution by Optical Spectroscopy and Computational Chemistry

et al. 2020

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Dacomitinib (PF-00299804) was recently approved by the Food and Drug Administration (FDA) as a tyrosine kinase inhibitor (TKI). Unfortunately, side effects and disease resistance eventually result from its use. Off-target effects in some kinase inhibitors have arisen from drug conformational plasticity; however, the conformational states of Dacomitinib in solution are presently unknown. To fill this gap, we have used computational chemistry to explore optimized molecular geometry, properties, and ultraviolet-visible (UV-Vis) absorption spectra of Dacomitinib in dimethyl sulfoxide (DMSO) solution. Potential energy scans led to the discovery of two planar and two twisted conformers of Dacomitinib. The simulated UV-Vis spectral signatures of the planar conformers reproduced the two experimental spectral bands at 275 and 343 nm in solution. It was further discovered that Dacomitinib forms conformers through its three flexible linkers of two C-NH-C bridges, which control the orientations of the 3-chloro-4-fluoroaniline ring (Ring C) and the quinazoline ring (Rings A and B) and the 4-piperidin-1-yl-buten-2-nal side chain, and one CO -C local bridge which controls the methoxy group locally. When in isolation, these flexible linkers form close hexagon and pentagon loops through strong intramolecular hydrogen bonding so that the "planar" conformers Daco-P1 and Daco-P2 are more stable in isolation. Such flexibility of the ligand and its ability to dock and bind with protein also depend on their interaction with the environment, in addition to their energy and spectra in isolation. However, an accurate quantum mechanical study on drug/ligand conformers in isolation provides necessary reference information for the ability to form a complex with proteins.

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“…Prognosis was dramatically improved in patients with advanced non-small cell lung cancer (NSCLC) harboring somatic activating EGFR mutations (EGFRm) who were treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) (2,3). Recently, in the FLAURA phase III study, EGFRm-positive patients with untreated advanced NSCLC who received osimertinib, a third-generation irreversible EGFR-TKI that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations, achieved a progression-free survival (PFS) and overall survival (OS) of 18.9 and 38.6 months, respectively, in comparison with gefitinib or erlotinib (4)(5)(6). However, progression is inevitable and immune checkpoint inhibitors (ICIs) have not achieved satisfactory outcomes after treatment with EGFR-TKIs.…”

mentioning

confidence: 99%

Oncogene addiction and immune escape: friends or foes?

Abdayem

Planchard

2020

Ann Transl Med

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The evolving first-line treatment of advanced non-small cell lung cancer harbouring epidermal growth factor receptor mutations

Cited by 6 publications

References 26 publications

Cost-Efficient and Easy to Perform PCR-Based Assay to Identify Met Exon 14 Skipping in Formalin-Fixed Paraffin-Embedded (FFPE) Non-Small Cell Lung Cancer (NSCLC) Samples

Cost-Efficient and Easy to Perform PCR-Based Assay to Identify Met Exon 14 Skipping in Formalin-Fixed Paraffin-Embedded (FFPE) Non-Small Cell Lung Cancer (NSCLC) Samples

Deducing the Conformational Properties of a Tyrosine Kinase Inhibitor in Solution by Optical Spectroscopy and Computational Chemistry

Oncogene addiction and immune escape: friends or foes?

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