A Novel EGFR Mutation in Exon 18 with High Sensitivity to EGFR TKI Treatment with Reduced Dose

Brandao, Erika Pereira; Pantarotto, Marcos; Cruz, Marcelo Rocha

doi:10.1097/jto.0b013e31826d8f66

Cited by 8 publications

(6 citation statements)

References 4 publications

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“…The most intriguing findings of our NGS studies were mutations of the EGFR gene in 22% of 27 MCC tumours, and overexpression of ALK and EZH2 at mRNA level in MCC tumours compared to normal skin . Most of the EGFR mutations we detected have been previously reported in non‐small‐cell lung cancer, and at least one of the mutations has been reported to be responsive to EGFR inhibitor treatment in lung adenocarcinoma . EGFR and ALK are transmembrane receptor tyrosine kinases involved in many types of cancer; for example, non‐small‐cell lung cancer .…”

Section: Introductionmentioning

confidence: 65%

ALK and EGFR expression by immunohistochemistry are associated with Merkel cell polyomavirus status in Merkel cell carcinoma

2019

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Aims: Merkel cell carcinoma, a rare cutaneous neuroendocrine tumour of the skin, can be categorised into two groups according to Merkel cell polyomavirus (MCV) presence. MCV-negative tumours are more aggressive and frequently associated with gene mutations. Some of the genes are potential therapeutic targets. We have previously reported EGFR mutations in six of 27 MCC tumours and overexpression of ALK and EZH2 at mRNA level in MCC tumours. In this study, we sought to determine expression of ALK, EGFR and EZH2 in MCC samples and assess their correlation to MCV status and clinical parameters. Methods and results: Tissue microarrays were utilised and stained with primary antibodies. Staining data were statistically compared to patient sex, tumour location and development of metastasis and MCC-specific death; 112 tumours and their corresponding patient data were included. We found strong expression of ALK in 51% and strong expression of EZH2 in 76% of the tumours. There was evident correlation of ALK expression with MCV-positivity. Expression of EGFR was infrequent, presenting only in seven MCVnegative tumours. None of the proteins associated with development of metastasis or MCC specific death. Conclusions: ALK and EZH2 expression are frequent in MCC and ALK expression correlates to MCV positivity. EGFR positive tumours might respond to EGFR inhibiting treatment.

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Section: Introductionmentioning

confidence: 65%

ALK and EGFR expression by immunohistochemistry are associated with Merkel cell polyomavirus status in Merkel cell carcinoma

2019

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“…Patients with LC, who have EGFR mutations, are normally treated with tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib and afatinib (86). However, sensitivity to TKI treatment varies with the type of EGFR mutation (87,88). Monoclonal antibodies and TKIs are usually applied to treat specific genetic alterations, including EGFR and ALK, in both the first line and resistant settings (89,90).…”

Section: Targeted Therapies Based On Non-invasive Detectionmentioning

confidence: 99%

Emerging non‑invasive detection methodologies for lung cancer (Review)

Shu

Yang

et al. 2020

Oncol Lett

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The potential for non-invasive lung cancer (LC) diagnosis based on molecular, cellular and volatile biomarkers has been attracting increasing attention, with the development of advanced techniques and methodologies. It is standard practice to tailor the treatments of LC for certain specific genetic alterations, including the epidermal growth factor receptor, anaplastic lymphoma kinase and BRAF genes. Despite these advances, little is known about the internal mechanisms of different types of biomarkers and the involvement of their related biochemical pathways during the development of LC. The development of faster and more effective techniques is essential for the identification of different biomarkers. The present review summarizes some of the latest methods used for detecting molecular, cellular and volatile biomarkers in LC and their potential use in clinical diagnosis and targeted therapy. Contents 1. Introduction 2. Emerging non-invasive detection technologies for lung cancer 3. Challenges and future directions

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“…Mutational analysis of EGFR showed a rare exon 18 mutation, which was available 4 weeks later. 17 Due to this delay, the patient underwent first-line chemotherapy with carboplatin AUC 6 intravenous (IV) D1, pemetrexed 500 mg/m 2 IV D1, and bevacizumab 15 mg/kg IV D1 every 3 weeks for four cycles, until December 2009, with partial response. In January 2010, erlotinib was introduced at a dose of 150 mg per day, with initial partial response.…”

Section: Case Reportsmentioning

confidence: 99%

Combination of afatinib with cetuximab in patients with EGFR-mutant non-small-cell lung cancer resistant to EGFR inhibitors

Gomes¹,

Cruz²

2015

OTT

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Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have shown effectiveness for advanced non-small-cell lung cancer (NSCLC) with activating mutations in the EGFR gene. However, resistance to the EGFR TKIs develops mostly secondary to T790M mutation in exon 20. The use of afatinib associated with cetuximab represents a new possibility of therapy following progression on gefitinib or erlotinib. We present two patients who acquired resistance to first-generation TKI and who underwent combination treatment with afatinib plus cetuximab as third-line therapy. Both patients presented partial response, and the time duration of disease control was 8 months and 10 months. The combined use of afatinib plus cetuximab emerges as a new possibility for the treatment of patients with advanced NSCLC harboring mutated EGFR after progression on first-generation EGFR TKIs with consequently acquired resistance to TKIs. Further studies are necessary to consolidate the data.

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A Novel EGFR Mutation in Exon 18 with High Sensitivity to EGFR TKI Treatment with Reduced Dose

Cited by 8 publications

References 4 publications

ALK and EGFR expression by immunohistochemistry are associated with Merkel cell polyomavirus status in Merkel cell carcinoma

ALK and EGFR expression by immunohistochemistry are associated with Merkel cell polyomavirus status in Merkel cell carcinoma

Emerging non‑invasive detection methodologies for lung cancer (Review)

Combination of afatinib with cetuximab in patients with EGFR-mutant non-small-cell lung cancer resistant to EGFR inhibitors

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