Afatinib and lung cancer

Jain, Prantesh; Khanal, Rashmi; Sharma, Aakanksha; Yan, Feng; Sharma, Neelesh

doi:10.1586/14737140.2014.983083

Cited by 16 publications

(12 citation statements)

References 51 publications

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“…EGFR signaling can be constitutively activate through genic mutation or genic amplification or both, which has been shown to be closely related to the occurrence, progression and poor prognosis of NSCLC [ 4 – 6 ]. Besides, there have studies demonstrated activation mutations in the tyrosine kinase domain of EGFR and this percentage of mutations may range from 15% to 40%, particularly common in Asian, female, never or light smoking NSCLC [ 7 – 10 ]. More than 90% of the known activating EGFR mutations are deletion of exon 19 (in-frame) and point mutation of exon 21 (L858R) [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer

et al. 2017

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After the discovery of activating mutations in EGFR, EGFR tyrosine kinase inhibitors (TKIs) have been introduced into the first-line treatment of non-small-cell lung cancer (NSCLC). A series of studies have shown that EGFR TKI monotherapy as first-line treatment can benefit NSCLC patients harbouring EGFR mutations. Besides, combination strategies based on EGFR TKIs in the first line treatment have also been proved to delay the occurrence of resistance. In this review, we summarize the scientific literature and evidence of EGFR TKIs as first-line therapy from the first-generation EGFR TKIs to conceptually proposed fourth-generation EGFR TKI, and also recommend the application of monotherapy and combination therapies of the EGFR-based targeted therapy with other agents such as chemotherapy, anti-angiogenic drugs and immunecheckpoint inhibitors.

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Section: Introductionmentioning

confidence: 99%

“…By irreversible covalent bond, it blocks enzymatic activity of active ErbB receptor family members. Because the irreversible covalent binding can inhibit the kinase activity until the synthesis of new receptors, the action time of afatinib may longer than reversible EGFR TKIs [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer

et al. 2017

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“…Non‐small cell lung cancer accounts for 80%‐85% of all lung cancers, and represents the leading cause of cancer‐related deaths in men and women worldwide . First‐generation EGFR TKI, gefitinib and erlotinib, and the second‐generation EGFR inhibitor afatinib, used as first‐line treatments for advanced NSCLC patients with EGFR‐activating mutations, have shown promising clinical results with superior progression‐free survival compared with platinum doublet chemotherapy regimens . Third‐generation EGFR inhibitors, such as AZD9291, have been developed with the aim of overcoming resistance induced by the EGFR T790M mutation, which occurs in approximately half of patients on EGFR‐TKI therapy that show disease progression .…”

Section: Introductionmentioning

confidence: 99%

SHR‐A1403, a novel c‐mesenchymal‐epithelial transition factor (c‐Met) antibody‐drug conjugate, overcomes AZD9291 resistance in non‐small cell lung cancer cells overexpressing c‐Met

Tong

Gao

et al. 2019

Cancer Science

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been used as the first‐line treatment of non‐small cell lung cancers (NSCLC) harboring EGFR‐activating mutations, but acquired resistance is ubiquitous and needs to be solved urgently. Here, we introduce an effective approach for overcoming resistance to the EGFR‐TKI, AZD9291, in NSCLC cells using SHR‐A1403, a novel c‐mesenchymal‐epithelial transition factor (c‐Met)‐targeting antibody‐drug conjugate (ADC) consisting of an anti‐c‐Met monoclonal antibody (c‐Met mAb) conjugated to a microtubule inhibitor. Resistant cells were established by exposing HCC827 to increasing concentrations of EGFR‐TKI. c‐Met was found to be overexpressed in most resistant cells. AZD9291 resistance was partially restored by combination of AZD9291 and crizotinib only in resistant cells overexpressing phospho‐c‐Met, which synergistically inhibited c‐Met‐mediated phosphorylation of the downstream targets ERK1/2 and AKT. In resistant cells overexpressing c‐Met, neither crizotinib nor c‐Met mAb was able to overcome AZD9291 resistance. In contrast, SHR‐A1403 strongly inhibited proliferation of AZD9291‐resistant HCC827 overexpressing c‐Met, regardless of the levels of c‐Met phosphorylation. SHR‐A1403 bound to resistant cells overexpressing c‐Met was internalized into cells and released associated microtubule inhibitor, resulting in cell‐killing activity that was dependent on c‐Met expression levels only, irrespective of the involvement of c‐Met or EGFR signaling in AZD9291 resistance. Consistent with its activity in vitro, SHR‐A1403 significantly inhibited the growth of AZD9291‐resistant HCC827 tumors and caused tumor regression in vivo. Thus, our findings show that SHR‐A1403 efficiently overcomes AZD9291 resistance in cells overexpressing c‐Met, and further indicate that c‐Met expression level is a biomarker predictive of SHR‐A1403 efficacy.

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“…Afatinib (Giotrif ® , BoehringerIngelheim): Afatinib is an anilinequinazoline derivative with a reactive acrylamide group which can modify the catalytic domains of EGFR, HER2, and ErbB-4, with orally bioavailable irreversible EGFR inhibitor and afatinibaction may longer than reversible EGFR TKIs [15,27].…”

Section: Second Generation Egfr Tk Inhibitorsmentioning

confidence: 99%

A Review: Status of Genetic Modulated Nonsmall Cell Lung Cancer Targets and Treatment (Current Updates in Drugs for Non-Small Cell Lung Cancer Treatment)

Kumar

Purohit

Dagar

2018

Asian J Pharm Clin Res

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Genetic modifications or mutations has been a bottleneck for the treatment of cancer; it is widely known to play a vital role in the progression of metastatic level/stage within the nonsmall cell lung cancer (NSCLC). The NSCLC of cancer is responsible for lung cancer lawsuits. In the various genetic mutations related study has been concluded with the various genes findings, which are named as the epidermal growth factor receptor, anaplastic lymphoma kinase, Kristen rat sarcoma virus, ROS proto-oncogene 1, human epidermal growth factor, B-RAF proto-oncogene, rearranged during Transfection, MET, Phosphatidyl 3-kinases CA, IGF-1R, NTRK1, FGFR1, and DDR2. The various research data supported this study. The involvement of the gene in the NSCLC patients made a paradigm shift in the drug discovery. The presence of one mutation in connection with some other could have an impact on NSCLC remedy.Utilizing this genotype-directed therapy for an advanced NSCLC has to turn out to be an appealing and efficacious treatment strategy. Here in the advancement of research, related genetic modulated targets and treatment have been discussed, particular genetic mutations help to find new updated interventions or medicinal drugs for the treatment of NSCLC. In there view, we have comprehensively arranged the mutation type and treatment with the status of NSCLC.

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Afatinib and lung cancer

Cited by 16 publications

References 51 publications

EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer

EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer

SHR‐A1403, a novel c‐mesenchymal‐epithelial transition factor (c‐Met) antibody‐drug conjugate, overcomes AZD9291 resistance in non‐small cell lung cancer cells overexpressing c‐Met

A Review: Status of Genetic Modulated Nonsmall Cell Lung Cancer Targets and Treatment (Current Updates in Drugs for Non-Small Cell Lung Cancer Treatment)

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