scholarly journals Current Approaches in NSCLC Targeting K-RAS and EGFR

2019 ◽  
Vol 20 (22) ◽  
pp. 5701 ◽  
Author(s):  
Veronica Aran ◽  
Jasminka Omerovic
Keyword(s):  
Treatment Options ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Response To Therapy ◽  
Small Cell Lung ◽  
Ras Mutations ◽  
Tk Inhibitors ◽  
Epidermal Growth ◽  
Nsclc Patients ◽  
Viral Oncogene Homolog

The research and treatment of non-small cell lung cancer (NSCLC) have achieved some important advances in recent years. Nonetheless, the overall survival rates for NSCLC remain low, indicating the importance to effectively develop new therapies and improve current approaches. The understanding of the function of different biomarkers involved in NSCLC progression, survival and response to therapy are important for the development of early detection tools and treatment options. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (K-RAS) are two of the main significant biomarkers for the management of NSCLC. Mutations in these genes were associated with development and response to therapies. For example, the use of small molecule tyrosine kinase (TK) inhibitors and immunotherapy has led to benefits in some, but not all patients with altered EGFR. In contrast, there is still no effective approved drug to act upon patients harbouring K-RAS mutations. In addition, K-RAS mutations have been associated with lack of activity of TK inhibitors. However, promising approaches aimed to inhibit mutant K-RAS are currently under study. Therefore, this review will discuss these approaches and also EGFR therapies, and hopefully, it will draw attention to the need of continued research in the field in order to improve the outcomes in NSCLC patients.

The quantification of epidermal growth factor receptor (EGFR) in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7597-7597
Author(s):  
C. Camps ◽  
R. Sirera ◽  
M. Muñoz-Navarro ◽  
G. Lopez-Vivanco ◽  
G. Alonso ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Complete Response ◽  
Binding Domain ◽  
Response To Therapy ◽  
First Line Therapy ◽  
Lower Egfr ◽  
Epidermal Growth ◽  
Nsclc Patients

7597 Background: EGFR has an extracellular ligand-binding domain that can be proteolitically cleaved from the cell surface and can be accurately quantified in blood by ELISA. We have investigated the usefulness of plasma EGFR measurements as prognostic marker in advanced NSCLC. Methods: The cohort consisted in 329 patients (p) with advanced NSCLC that received first-line therapy with cisplatin and docetaxel. The concentration levels of the EGFR extracellular binding domain were determined by a sandwich quantitative ELISA in the baseline, before therapy. Results: Median age was 61, range [39–80], 84% males, 100% caucasian, 68% stage IIIB and 32% IV and 99% PS 0–1. The histological subtypes were: 31% squamous cell carcinoma, 49% adenocarcinoma, 15% large cell, and 5% undifferentiated. 181 p achieved complete response (CR), partial response (PR) or stable disease (SD) and 109 p progressive disease (PD). Median patient's plasma levels of EGFR were 32.4 ng/ml. There were not differences in p according to histology, site of metastasis and ECOG. There were differences in response to therapy; CR+PR+SD p presented median EGFR of 31.97 ng/ml [13.2–48.6] vs 30 ng/ml [16.9–46.8] in the PD group (p=0.024). Dividing the cohort in two sets according to EGFR median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with EGFR<32.4 ng/ml had a median TTP of 3.9 months (m) [3.3–4.6] while for EGFR>32.4 ng/ml was 4.7 m [4.0–5.4], (p=0.024). OS when EGFR<32.4 ng/ml was 6.9 m [5.9–7.8] and for EGFR>32.4 ng/ml was 9.1 m [8.2–10.1], (p=0.038). Conclusions: Patients with PD presented significantly lower levels of serum EGFR than those patients with CR+PR+SD. There is a relationship among lower EGFR concentration in serum with a worst prognosis in advanced NSCLC p in terms of TTP and OS. No significant financial relationships to disclose.

Further evaluation of 11C-PD153035 as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in non-small cell lung cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3590-3590
Author(s):  
J. Yu ◽  
N. Liu ◽  
M. Hu ◽  
X. Song ◽  
L. Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Expression Level ◽  
Tumor Mass ◽  
Epidermal Growth ◽  
Nsclc Patients ◽  
Exon 19

3590 Background: Epidermal growth factor receptor (EGFR) plays a key role in tumorgenosis and is therefore an important target for new therapeutic and prognostic strategies. Our pilot study has demonstrated that 11C-PD153035, a highly EGFR selective tracer for positron emission tomography (PET), accumulated in tumor mass of non-small cell lung cancer (NSCLC) and the tracer uptake correlated with EGFR expression. Here, we further evaluate correlation between the intensity of 11C-PD153035 uptake and EGFR protein expression level and gene mutation. Methods: Fourteen patients (45–71y, mean 59.2±9.2 y, Male: Female = 8:6, squamous carcinoma: adenocarcinoma = 9:5) with pathologically proved NSCLC were examined with PET using 11C-PD153035 one week before surgery. Radioactivity concentrations, derived from regions of interest (ROI), were analyzed mathematically to maximum standardized uptake value (SUVmax). The EGFR protein expression of surgical specimen was utilized by immunohistochemistry (IHC) with a three-tier system intensity scored and Western Blot assay. The EGFR genetic alterations in exon 19 and 21 were examined by direct sequencing of polymerase chain reaction (PCR) products. Results: 11C-PD153035 uptake was observed in 9 out of 14 NSCLC patients (mean SUV 3.94±1.06, range 0.8–5.9) and the biodistribution study further demonstrated accumulation of radioactivity in the tumor mass. The SUVmax of 11C-PD153035 molecular images did not correlate with tumor size and injection dose of the tracer. A closely correlation between SUVmax and EGFR protein expression as determined by IHC (r = 0.84, p = 0.005) was observed but not with the protein expression level of Western Blot analysis (r = 0.442, p = 0.114), as well as EGFR exon 19 (r = -0.078, p = 0.790) or exon 21 (r = 0.118, p = 0.689) gene mutation. With ROC analysis according to IHC intensity, the cut-off value of SUVmax was 2.45. Conclusions: PET with 11C-PD153035 might therefore be used to visualize EGFR pattern on tumor in NSCLC patients and for individualized planning of therapeutic strategies with EGFR targeted drugs, especially small-molecule TKIs (gefitinib and erlotinib) which targeting the intracellular EGFR tyrosine kinase domain as PD153035. No significant financial relationships to disclose.

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