## 6 G-Protein-Coupled Estrogen Receptors and Non-Small Cell Lung Cancers  
In 1997, [PERSON] and colleagues discovered an estrogen-bound transmembrane receptor in breast cancer tissue [151]. In the same year, [PERSON] and colleagues [152] and, subsequently in 2005, [PERSON] and group [153] cloned the G-protein-coupled estrogen receptor cDNA sequence using differential cDNA library analysis of the human breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. In 2007, the International Union of Basic and Clinical Pharmacology officially named this molecule a G-protein-coupled \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Clinical Trial Registry** & **Primary Objective of the Trial** & **Phase of Study, Tumor Stage** & **Findings Published (Ref.)** \\ \hline NCT01556191 & Evaluating an EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib and an EGFR-TKI-anti-oestrogen (erlotinib, fulvestrant) combined potency in women with advanced-stage & Phase I, stage IV lung cancer, completed & Improved outcome [143] \\ \hline NCT00100854 & Evaluation of synergistic fulvestrant delivery with erlotinib for the non-small cell lung cancer (NSCLC) treatment & Phase II, stage IIIB or IV non-small cell lung cancer, completed & Improved outcome [144] \\ \hline NCT02666105 & Evaluation of adding exemestane therapy in postmenopausal women suffering from NSCLC while on treatment with an immune checkpoint antibody (pembrolizumab, atzolizumab or nivolumab) & Phase II, advanced stage NSCLC, ongoing & Improved outcome [145] \\ \hline NCT01664754 & Determining the safety and tolerability of escalating exemestane doses on being co-delivered with permereved non-squamous & Phase I, stage IV non-squamous NSCLC, ongoing & Combination is safe and well-tolerated, response rate correlates with tumor aromatase expression \\ \hline NCT02751385 & Screening the effect of nintendanib on the (ethinylestradioliol + levomorgestrel) pharmacokinetics in NSCLC patients & Phase I, all NSCLC patients, completed & No findings published todate \\ \hline NCT02751385 & Screening the effect of nintendanib on the (ethinylestradioliol + levomorgestrel) pharmacokinetics in NSCLC patients & Phase I, all NSCLC patients, completed & CT-103 did not provide superior survival over the \\ \hline NCT02751385 & Screening the effect of paclitaxel poliglumex (CT-103)/carboplatin versus paclitaxel/carboplatin for women NSCLC sufferers & Phase III, sufferers having \(>\)25 pg:mL-1 estradiol, completed & paclitaxel- carboplatin for first-line treatment of NSCLC patients, results were comparable for progression-free and overall survival [147] \\ \hline NCT03099174 & Ascertaining a safe dosage of xenutzumab in combination with abemaciclib with or without hormonal therapies in lung and breast cancer & Phase I, no stage distinction, ongoing & Findings not yet published \\ \hline NCT00592007 & Screening the impact of adding fulvestrant to erlotinib in NSCLC patients & Phase II, stage IIIB or IV, concluded & [148] \\ \hline NCT00932152 & Fulvestrant and anastomogle (aromatase inhibitor) as consolidation therapy in postmenopausal women NSCLC sufferers & Phase II, advanced stage NSCLC, concluded & [149] \\ \hline NCT01594398 & Assessing the food effect on entinostat pharmacokinetics in NSCLC sufferers (ENCOREE110) & Phase I, no stage distinction, completed & No findings published, study listed from [141] \\ \hline AM2013-4664 & Evaluation of erlotinib antitumor activity in NSCLC on fulvestrant inclusion in the patients received \(>\) 1 chemotherapy regimen & Phase II, advanced state NSCLC patients & [150] \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Current progress of clinical trials aimed toward using estrogen-expression-targeted non-small cell lung cancer treatment. estrogen receptor (GPER, also known as GPER1 or GPR30) [154]. Chromosomal mapping shows the human GPER gene being located on chromosome 7, containing a 1128 bp open reading frame that encodes a 375-amino acid receptor protein [151; 155]. GPER is a seven-transmembrane-bound ER [44].