moreover , there are no blood markers for the early detection of lung cancer ( unlike for cancers such as prostate , colorectal , and gynecological cancers ) ( 1 ) . in the past , non - specific cytotoxic agents were the first choice of treatment for patients with stage iv non - small - cell lung cancer ( nsclc ; either adenocarcinoma or squamous cell carcinoma ) ( 2 , 3 ) .  
however , in the last decade , novel molecular pathways have been found to be involved in adenocarcinoma and squamous cell carcinoma of the lung , and , as a result , targeted treatments are now being used .
the most important of these are the treatments that target the epidermal growth factor receptor ( egfr ) , anaplastic lymphoma kinase ( alk ) , serine / threonine - protein kinase b - raf ( braf ) , proto - oncogene tyrosine - protein kinase ros ( which is encoded by the ros1 gene ) , c - met proto - oncogene protein ( which is encoded by the met gene ) , and ret proto - oncogene protein ( which is encoded by the ret gene found on chromosome 10 ) ( 4 , 5 ) .
an issue that has yet to be clarified is whether these targeted treatments are effective against eye metastasis .
this issue is discussed in the following section , which is based on data that were obtained via a search of the us national center for biotechnology information s pubmed service on february 19 , 2017 .
overview of the use of targeted treatments in relation to eye metastasis currently , oral tyrosine kinase inhibitors ( tkis ) are being used to treat egfr- and alk - positive patients . in particular , for egfr - positive patients , erlotinib , gefitinib , and afatinib ( the first two of which are first - generation tkis that target egfr , and the third of which is a second - generation tki that targets egfr ) are the treatments of choice .
if an egfr - positive patient being treated with tki experiences a relapse ( as assessed using the response evaluation criteria in solid tumors ( recist ) ( 6 ) ) , a rebiopsy should be performed ( 7 ) . however , if the patient s condition does not allow for a rebiopsy , a liquid biopsy should be performed ( 8) . in particular ,
if the egfr t790 m mutation is detected , osimertinib ( a tki that targets egfr ) should be administered ( 9 ) .  
research indicates that gefitinib could be an effective agent against choroidal metastasis , and it should be used if such a metastasis exists ( 10 ) . in the case of brain metastasis , research indicates that afatinib may be effective as a first - line treatment ( 11 ) .
furthermore , a recent study showed that osimertinib was rapidly effective against brain metastasis , and it negated the need for radiotherapy ( 12 ) . regarding patients with alk mutations , crizotinib ( a tki that targets alk ) is used as the first - line treatment ( 13 ) .
in particular , crizotinib has been shown to be effective against uveal and choroidal metastasis ( 14 , 15 ) .
the human epidermal growth factor receptor 2 ( her2 ) has been found to be overexpressed in patients with lung cancer ( 16 ) and , in these cases , trastuzumab ( a monoclonal antibody that targets her2 ) may be administered ( 17 ) .
research has indicated that this drug is able to control ocular metastasis ( 18 ) . however , it is important to take into consideration that fact that trastuzumab can also induce adverse ocular effects ( 19 ) .  
in addition to alk mutations , braf mutations have been observed in patients with lung cancer ( 20 ) . in these cases ,
the patients could be treated with ipilimumab ( a monoclonal antibody that targets cytotoxic t - lymphocyte - associated protein 4 ( ctla-4 ) ) . in particular , ipilimumab has been successfully used for uveal metastasis ( 20 - 24 ) . however , orbital myositis and retinopathy have been observed in patients treated with ipilimumab ( 22 , 23 ) , and other immunotherapies such as nivolumab and pembrolizumab ( both of which are monoclonal antibodies that target programmed cell death protein 1 ( pd-1 ) ) are currently being tested ( 20 , 21 ) .   in some patients with lung cancer , the ros1 pathway has been found to be upregulated ( 25 ) . in these cases ,
furthermore , research has indicated that eye metastasis that involves ros1 upregulation can be efficiently controlled with crizotinib ( 14 ) .
alternatively , cabozantinib ( a tki that targets c - met and vascular endothelial growth factor receptor 2 ( vegfr-2 ) ) can be used in cases involving crizotinib resistance ( 27 ) .  
the ret pathway has also been found to be upregulated in some patients with lung cancer ( 25 ) . in these cases ,
crizotinib ( a tki that targets alk and ros1 ) or alectinib ( a tki that targets alk ) should be administered ( 28 , 29 , 30 ) cabozantinib may also be effective ( 31 ) .  
lastly , the c - met pathway has been also shown to be upregulated in some patients with lung cancer ( 32 ) .
furthermore , a previous study has suggested that , in patients with melanoma , c - met overexpression is associated with uveal metastasis , but more data are required to clarify this association ( 34 ) .
a previous study indicated that crizotinib is effective against uveal metastasis that involves the upregulation of the c - met pathway in a melanoma model ( 15 ) .
however , for nsclc , cabozantinib should be used in cases involving upregulation of the c - met pathway ( 33 ) .
overall , the data on the use of tkis or immunotherapy to control eye metastasis are limited . we recommend that if a patient experiences a cancer relapse , biopsies should be taken from the sites of relapse .
we are currently waiting for trials with larger numbers of patients with braf , met , ret , and ros mutations . in these trials , data with the control of eye metastasis
should be collected so that clear conclusions can be drawn regarding the optimum treatment approaches .
all the aforementioned authors met the international committee of medical journal editors ( icmje ) criteria for authorship for this manuscript , take responsibility for the integrity of the work as a whole , and have provided approval for the revised manuscript to be published .
all the aforementioned authors met the international committee of medical journal editors ( icmje ) criteria for authorship for this manuscript , take responsibility for the integrity of the work as a whole , and have provided approval for the revised manuscript to be published .
 lung cancer remains the leading cause of death due to cancer . 
 we do not have effective tools for the early detection of lung cancer , so patients are usually diagnosed at an advanced stage . 
 however , novel therapies based on molecular pathways ( such as those involving the epidermal growth factor receptor , anaplastic lymphoma kinase , serine / threonine - protein kinase b - raf , proto - oncogene tyrosine - protein kinase ros , c - met proto - oncogene protein , and ret proto - oncogene protein ) are now commonly used in the treatment of lung cancer . in particular , these therapies are considered as first - line treatments for non - small - cell lung cancer . 
 this manuscript outlines previous research on these targeted treatments , focusing on whether they are effective against eye metastasis . 
INTRODUCTION
DISCUSSION
DISCLOSURE
Conflict of interest