scholarly journals Affibody-Modified Gd@C-Dots with Efficient Renal Clearance for Enhanced MRI of EGFR Expression in Non-Small-Cell Lung Cancer

2020 ◽  
Vol Volume 15 ◽  
pp. 4691-4703 ◽  
Author(s):  
Yongyi Wu ◽  
Haoxiang Li ◽  
Yuling Yan ◽  
Kai Wang ◽  
Yongna Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Renal Clearance ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Enhanced Mri ◽  
Egfr Expression

scholarly journals The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4443
Author(s):  
Nele Van Der Steen ◽  
Karen Zwaenepoel ◽  
Giulia Mazzaschi ◽  
Rosa A. Luirink ◽  
Daan P. Geerke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Egfr Mutations ◽  
Primary Therapy ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Egfr Expression

The c-Met receptor is a therapeutically actionable target in non-small-cell lung cancer (NSCLC), with one approved drug and several agents in development. Most suitable biomarkers for patient selection include c-Met amplification and exon-14 skipping. Our retrospective study focused on the frequency of different c-Met aberrations (overexpression, amplification and mutations) in 153 primary, therapy-naïve resection samples and their paired metastases, from Biobank@UZA. Furthermore, we determined the correlation of c-Met expression with clinicopathological factors, Epidermal Growth Factor Receptor (EGFR)-status and TP53 mutations. Our results showed that c-Met expression levels in primary tumors were comparable to their respective metastases. Five different mutations were detected by deep sequencing: three (E168D, S203T, N375S) previously described and two never reported (I333T, G783E). I333T, a new mutation in the Sema(phorin) domain of c-Met, might influence the binding of antibodies targeting the HGF-binding domain, potentially causing innate resistance. E168D and S203T mutations showed a trend towards a correlation with high c-Met expression (p = 0.058). We found a significant correlation between c-MET expression, EGFR expression (p = 0.010) and EGFR mutations (p = 0.013), as well as a trend (p = 0.057) with regards to TP53 mutant activity. In conclusion this study demonstrated a strong correlation between EGFR mutations, TP53 and c-Met expression in therapy-naïve primary resection samples. Moreover, we found two new c-Met mutations that warrant further studies.

scholarly journals Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Aiko Yamaguchi ◽  
Arifudin Achmad ◽  
Hirofumi Hanaoka ◽  
Yusri Dwi Heryanto ◽  
Anu Bhattarai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pet Imaging ◽  
Small Cell ◽  
Expression Level ◽  
Tumor Uptake ◽  
Small Cell Lung ◽  
Non Invasive ◽  
Egfr Expression

Abstract Backgrounds Overexpression of epidermal growth factor receptor (EGFR) has been established as a valid therapeutic target of non-small cell lung cancer (NSCLC). However, the clinical benefit of cetuximab as an EGFR-targeting drug is still controversial, partially due to the lack of effective means to identify suitable patients. This study aimed to investigate the potential of radiolabeled cetuximab as a non-invasive tool to predict cetuximab accumulation in NSCLC tumor xenografts with varying EGFR expression levels. Methods The NSCLC tumors in model mice were subjected to in vivo biodistribution study and positron emission tomography (PET) imaging 48 h after injection of either 111In- or 64Cu-labeled cetuximab. The EGFR expression levels of NSCLC tumors were determined by ex vivo immunoblotting. Results We found that tumors with high EGFR expression had significantly higher [111In]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [111In]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [64Cu]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [64Cu]Cu-DOTA-cetuximab allowed clear visualization of tumors. Conclusion Our findings suggest that this immuno-PET imaging can be clinically translated as a tool to predict cetuximab accumulation in NSCLC cancer patients prior to cetuximab therapy.

Prognostic significance of immunohistochemical markers in non-small cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7211-7211
Author(s):  
D. Renouf ◽  
R. Wood-Baker ◽  
D. Ionescu ◽  
S. Leung ◽  
H. Massoudi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Female Ratio ◽  
Egfr Expression

7211 Background: The purpose of this study is to use a large patient population to identify immunohistochemical (IHC) biomarkers to enable improved prognostication in patients with non-small cell lung cancer (NSCLC). Methods: A tissue microarray was constructed using duplicate 0.6 mm cores of formalin-fixed paraffin embedded tissue blocks from 609 patients with NSCLC. IHC was used to detect 11 biomarkers including EGFR, HER2, HER3, p53, p63, Bcl-1, Bcl-2, TTF-1, CEA, Ch, and SNP. A clinical database was created prospectively at the time of tissue collection. Survival outcomes were obtained from a Provincial Cancer Registry database. Results: Male to female ratio was 400:209; median age 63yrs (range 35–82); median survival 3.5yrs (mean 5.7). All specimens were reviewed: 243 adenocarcinoma (ACA), 272 squamous cell carcinoma (SCC), 35 large cell carcinoma, 32 non-small cell carcinoma NOS, and 6 other (giant cell carcinoma). 21 patients with other histologies were excluded. Survival data for 535 cases was available. As of June 2005, 429 patients (80%) had died; of these 286 (54%) died of lung cancer, 117 (22%) died of other known causes, and for 26 (5%) the cause of death was not available. Bcl-2 (p = 0.007) was the only biomarker to predict better overall survival (OS). Bcl-2 (p = 0.021) and p63 (p = 0.025) were significant for disease specific survival (DSS) in all NSCLC. Analysis of the subgroups indicated that p63 was significant (p = 0.039) for DSS in squamous cell carcinoma (SCC) but not for adenocarcinoma (ACA) (p = 0.81). Bcl-2 was not significant for DSS in either subgroup (p = 0.28 for SCC, p = 0.112 for ACA). EGFR expression was associated with improved DSS in SCC (p = 0.012) but not for ACA. Co-expression of EGFR-HER3 was more likely in SCC then in ACA (p = 0.033). There was no correlation between outcome and any combination or clustering of biomarkers. Conclusions: The biomarkers p63 and Bcl-2 are predictive of DSS in NSCLC. EGFR expression is predictive of DSS in SCC. Sub-classification of NSCLC by histopathology is important as the relevance of some biomarkers (EGFR) would be lost if pooled. p63, Bcl-2, and EGFR may be used as prognostic markers in patients with NSCLC. Co-expression of EGFR-HER3 is more likely in SCC then in ACA. This may help explain the differential response to EGFR inhibitors in SCC versus ACA. No significant financial relationships to disclose.

IMRT and cetuximab in stage 3 non-small cell lung cancer: The NEAR trial (NCT00115518)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18168-18168 ◽  
Author(s):  
A. D. Jensen ◽  
M. W. Münter ◽  
H. G. Bischoff ◽  
E. Herpel ◽  
R. Haselmann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Lung Function ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Combined Treatment ◽  
Small Cell ◽  
Combined Modality Treatment ◽  
Small Cell Lung ◽  
Egfr Expression

18168 Background: For stage 3 non-small cell lung cancer (NSCLC), RCHT is the treatment of choice with sometimes marked side- effect. Hence, patients with co-morbidities may not be eligible for combined treatment. Based on the results at other tumor sites, a combined- modality treatment with the EGFR antibody cetuximab and IMRT should be evaluated in a prospective phase II trial. Methods: Pts with inoperable stage 3 NSCLC ineligible for RCHT are included in the trial. Treatment consists of cetuximab weekly and concurrent IMRT with 50 Gy to CTV and subsequent boost to GTV to 66 Gy. Staging and f/u include CT, FDG-PET, and lung function prior to/after completion of treatment (response assessment) plus CT scans in 3 mo intervals. Overall treatment time is 4 months. Side-effects and efficacy were assessed. Results: So far, 17 of 30 pts (median 70 yrs; 57–82 yrs) have been enrolled. The median f/u from treatment start was 6 months (1–17). 3 pts are still being treated, 13 pts have completed, and one pt died prior to completion of treatment. Where available, EGFR staining yielded a median receptor score of 2 (0–3) in 12 pts. 3/12 pts showed strong (3+), 2/12 showed no EGFR expression. The treatment was well tolerated with only 1 treatment-related °3 morbidity (esophagitis). All pts showed acneiforme skin rash (°I), but no significant reduction of lung function. 2 pts with underlying heart disease developed thrombembolic complications (arterial & pulmonary embolisms). We observed PR in 10/13 and SD in 3/13 pts (RECIST). All pts showed a marked reduction of SUV in PET even if CT did not show PR. Conclusion: Preliminary results of IMRT combined with cetuximab suggest a reasonably safe treatment with only mild side-effects and encouraging local response. Addition of cetuximab does not seem to increase toxicity of RT. [Table: see text]

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