Predictive Molecular Markers: Has the Time Come for Routine Use in Lung Cancer?

2004 ◽  
Vol 2 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Angela M. Davies ◽  
Philip C. Mack ◽  
Primo N. Lara ◽  
Derick H. Lau ◽  
Kathleen Danenberg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Markers ◽  
Excision Repair ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Taxane Resistance ◽  
Molecularly Targeted Agents ◽  
Epidermal Growth ◽  
Pathway Inhibition ◽  
Nsclc Patients

Although some evidence exists to support the use of clinical factors such as performance status and weight loss to predict response and toxicity to therapy in non-small cell lung cancer (NSCLC) patients, researchers have shown little prospective data on the use of molecular markers to facilitate selection of specific chemotherapy or new molecularly targeted agents in this patient population. Breast cancer exemplifies the growing role that molecular markers are playing, not only as prognostic factors, but also in predicting response to targeted treatments such as hormonal therapy, and more recently, trastuzumab (Herceptin). Although several studies have examinedmolecular markers in lung cancer and have shown promising potential value, these studies were retrospective and require prospective validation. To identify molecular markers that reliably predict response and to be able to individualize cytotoxic and targeted therapy for NSCLC patients are the ultimate goals of future trials. This article focuses on a selected number of promising markers under study in lung cancer, including those thought to play roles in response to DNA damaging chemotherapy (excision repair cross-complementing [ERCC1], xeroderma pigmentosum group D [XPD]), taxane resistance (-tubulin III), antimetabolite therapy (RRM1), irinotecan metabolism (UGT1A1) and epidermal growth factor receptor (EGFR) pathway inhibition. To date, none of these markers can be recommended for routine use in clinical practice.

scholarly journals Epidermal growth factor receptor protein expression in lung cancer and survival analysis

2018 ◽  
Vol 5 (3) ◽  
pp. 550
Author(s):  
Shivalingaswamy Salimath ◽  
Jayaraj B. S. ◽  
Mahesh P. A. ◽  
M. D. Majeed Pasha ◽  
Lokesh K. S. ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Multivariate Analysis ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Nsclc Patients

Background: Epidermal Growth Factor Receptor (EGFR) is one of the important molecules involved in lung cancer initiation and progression. Studies on over expression of EGFR and its survival in relation with Non-small cell lung cancer (NSCLC) patients have yielded controversial results. Prevalence of EGFR expression in NSCLC patients and 6-month survival in south Indian population is unknown.Methods: We carried out a prospective study in tertiary hospital. Diagnosed patients with NSCLC were included in the study and were interviewed with questionnaire containing demography and investigations like Chest X-ray, CT thorax, Bronchoscopy were recorded. EGFR expression analysis was done for all patients and were followed up monthly for 6 months and details of survival and treatment were collected. Cox regression analysis was used to assess their survival.Results: 50 patients with NSCLC were included. Forty-four (88%) were men, median age of study group was 65 years. Twenty-seven patients (54%) had Adenocarcinoma, 14 patients (28%) had Squamous cell carcinoma, 7 patients (14%) had poorly differentiated carcinoma and 2 patients (4%) had large cell carcinoma. Thirty-four (68%) samples were positive for EGFR expression. On multivariate analysis we found patients who took chemotherapy and with good performance status (Karnofsky score >65 and Eastern Cooperative Oncology Group >2.5) had better survival at 6 months.Conclusions: Patients with EGFR positivity had better survival with chemotherapy but worse with radiotherapy. Patients who took chemotherapy and had good performance status had better survival on multivariate analysis. We didn’t find any correlation between EGFR positivity and poor survival.

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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