scholarly journals A small-molecule compound D6 overcomes EGFR-T790M-mediated resistance in non-small cell lung cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiaolong Tang ◽  
Lizhi Cheng ◽  
Guo Li ◽  
Yong-Ming Yan ◽  
Fengting Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Cell Growth And Migration ◽  
Small Molecule Compound ◽  
Egfr Tki

AbstractNon-small cell lung cancer (NSCLC) is a deadly and highly prevalent malignancy. Targeting activated-EGFR mutations in NSCLC via EGFR tyrosine kinase inhibitor (EGFR-TKI) initially achieves a profound therapeutic response, but resistance frequently evolves, reducing treatment options. Here, we present a small-molecule compound D6 which selectively inhibits tumor cell growth and migration in NSCLC cells with EGFR-TKI-resistant T790M-EGFR-activated mutations (T790M-EGFR-AM), e.g., L858R/T790M, 19Del/T790M and L858R/T790M/C797S. D6 mimics a natural product isolated from the roots of Codonopsis pilosula and selectively competes with T790M-EGFR-AM to bind to HSP90, thus facilitating the ubiquitination dependent proteasomal degradation of T790M-EGFR-AM. By contrast, D6 has little impact on typical HSP90 chaperone activity, suggesting low systemic toxicity. Promisingly, D6 combined with erlotinib or osimertinib shows efficacy in overcoming the EGFR-TKIs-resistance in NSCLCs. Our study raises an alternative strategy to overcome T790M-mediated EGFR-TKI resistance in NSCLC via targeting the protein–protein interaction of HSP90 and T790M-EGFR by intervention with D6.

scholarly journals Post-Progression Survival after EGFR-TKI for Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135393 ◽  
Author(s):  
Yoshihito Kogure ◽  
Hideo Saka ◽  
Masahide Oki ◽  
Toshiki I. Saito ◽  
Shimaa Nour Moursi Ahmed ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Egfr Tki

Analysis of the EGFR mutations in non-small cell lung cancer patients after EGFR-TKI treatment.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e18065-e18065
Author(s):  
H. Yamaguchi ◽  
T. Ikeda ◽  
N. Tomonaga ◽  
H. Nakano ◽  
T. Kitazaki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Tki Treatment ◽  
Egfr Tki

scholarly journals Afatinib in advanced pretreated non-small-cell lung cancer— a Canadian experience

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
D. A. Ezeife ◽  
B. Melosky ◽  
R. Tudor ◽  
S. Lin ◽  
A. Lau ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Pretreated Patients ◽  
Egfr Tki

Background Afatinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (egfr tki), is approved for first-line therapy in advanced EGFR mutation–positive non-small-cell lung cancer (nsclc) and has previously demonstrated activity after failure of chemotherapy and reversible egfr tkis, with improved response and progression-free survival, compared with placebo. Outcomes in pretreated patients with advanced nsclc receiving afatinib through a Canadian special access program (sap) are reported here.MethodsPatients with nsclc progressing after at least 1 line of chemotherapy and an egfr tki were eligible to enroll in the sap. Characteristics of patients from the two largest accruing Canadian centres were retrospectively reviewed, including demographics, disease and treatment data, and patient outcomes.ResultsThe 53 patients who received afatinib (57% women, 51% never-smokers, 26% of East Asian ethnicity, and 66% with adenocarcinoma) had a median age of 59 years. EGFR mutations were documented in 25%, and EGFR wildtype in 8%. All patients had received prior egfr tki treatment, with 42% achieving a response. Patients took afatinib for a median of 2 months (range: 0–26 months); 17% required 1 or more dose reductions. Of 47 evaluable patients receiving afatinib, 10 experienced tumour shrinkage, and 11, stable disease. Median survival from afatinib initiation was 5 months (95% confidence interval: 2 months to 8 months). Grade 3 or greater diarrhea, rash, paronychia, and stomatitis were seen in 9%, 11%, 6%, and 4% of patients respectively.ConclusionsIn an unselected population of pretreated patients with advanced nsclc after tki failure, median survival with afatinib therapy was 5 months. Through a sap, afatinib demonstrated activity in clinical practice, with manageable toxicity.

Optimal Adjuvant Therapy in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer Harboring EGFR Mutations

2020 ◽  
Vol 43 (12) ◽  
pp. 686-693
Author(s):  
Miaomiao Wen ◽  
Lei Wang ◽  
Xuejiao Wang ◽  
Sanhu Yang ◽  
Ying Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Stage Iiia ◽  
Egfr Tki ◽  
Egfr Tkis

<b><i>Background:</i></b> Some non-small-cell lung cancer (NSCLC) patients are unexpectedly diagnosed with stage IIIA-N2 disease at the time of thoracoscopy or thoracotomy. Because of the limited statistical evidence of induction chemotherapy for these patients, it is necessary to develop more profound treatment strategies. <b><i>Methods:</i></b> The demographic and clinical characteristics of patients with stage IIIA-N2 NSCLC harboring epidermal growth factor receptor (EGFR) mutations after radical resection were retrospectively reviewed. The patients were divided into 3 groups based on treatment: EGFR tyrosine kinase inhibitors (EGFR-TKIs, erlotinib or gefitinib), adjuvant chemotherapy (docetaxel plus cisplatin), and combination treatment (chemotherapy plus EGFR-TKIs). The effect of adjuvant therapy on survival rate was assessed using univariate and Cox regression analyses. <b><i>Results:</i></b> Patients receiving EGFR-TKIs alone showed significantly improved disease-free survival (DFS; <i>p</i> = 0.025) when compared to those receiving chemotherapy alone. Compared to chemotherapy alone, the combination of chemotherapy and EGFR-TKIs resulted did not significantly improve DFS (<i>p</i> &#x3c; 0.001) and overall survival (OS <i>p</i> &#x3c; 0.001). The combination of EGFR-TKIs with chemotherapy as adjuvant therapy led to improvements in both DFS (<i>p</i> = 0.116) and OS (<i>p</i> = 0.039) compared to patients receiving a EGFR-TKI monotherapy. Toxicities were mild in the 3 treatment groups. <b><i>Conclusions:</i></b> Our study demonstrated that adjuvant EGFR-TKI treatment significantly increased the DFS of patients with stage IIIA-N2 NSCLC when compared with cisplatin-based chemotherapy. The use of EGFR-TKIs and chemotherapy is recommended in the setting of combined-modality therapy.

scholarly journals Inhibition of the Growth Factor MDK/Midkine by a Novel Small Molecule Compound to Treat Non-Small Cell Lung Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71093 ◽  
Author(s):  
Huifang Hao ◽  
Yutaka Maeda ◽  
Takuya Fukazawa ◽  
Tomoki Yamatsuji ◽  
Munenori Takaoka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Small Molecule Compound

scholarly journals A novel small-molecule compound diaporine A inhibits non-small cell lung cancer growth by regulating miR-99a/mTOR signaling

2014 ◽  
Vol 15 (10) ◽  
pp. 1423-1430 ◽  
Author(s):  
Yuxian Song ◽  
Huan Dou ◽  
Ping Wang ◽  
Shuli Zhao ◽  
Tingting Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Mtor Signaling ◽  
Cancer Growth ◽  
Small Cell Lung ◽  
Small Molecule Compound

scholarly journals PD-L1 Expression and Outcome in Patients with Metastatic Non-Small Cell Lung Cancer and EGFR Mutations Receiving EGFR-TKI as Frontline Treatment

2021 ◽  
Vol Volume 14 ◽  
pp. 2301-2309
Author(s):  
Cheng-Yu Chang ◽  
Yi-Chun Lai ◽  
Yu-Feng Wei ◽  
Chung-Yu Chen ◽  
Shih-Chieh Chang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Frontline Treatment ◽  
Egfr Tki
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