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• W2956124859 abstract "Abstract Lung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC), which accounts for 85% of all lung cancer cases, includes adenocarcinoma, squamous cell lung carcinoma and large-cell lung carcinoma. Despite recent advances in targeted therapies for adenocarcinoma, they are effective in only a small percentage of patients while there are no targeted therapies available for squamous cell lung cancer. Therefore, it is critical to identify novel intervention strategies against NSCLC. In the present study, we have identified connective tissue growth factor (CTGF) as a possible therapeutic target for NSCLC. CTGF is an extracellular-matrix (ECM) associated protein, which is involved in cellular processes like cell adhesion, migration, proliferation, differentiation, survival, apoptosis and senescence. CTGF has been associated with both oncogenic as well as tumor suppressive activities in context of different cancer types. The function of CTGF in lung cancer pathogenesis remains controversial. We performed immunohistochemistry on tissue microarray containing 60 cases, which clearly suggested that CTGF expression increases in lung carcinoma. More specifically, among other subtypes, squamous cell lung cancer cases expressed more CTGF compared to their matched normal tissues. To determine the functional role of CTGF in NSCLC, we employed both genetic and pharmacologic approaches to inhibit CTGF activity. Our results clearly demonstrated that CTGF inhibition by both lentiviral knockdown as well as monoclonal antibody against CTGF (FG-3019) caused marked inhibition in cell proliferation, colony formation and xenograft growth in immunodeficient mice. We have also found that CTGF knockdown causes cell cycle arrest and apoptosis. Furthermore, we tested the efficacy of FG-3019 along with drugs like cisplatin and gemcitabine in patient-derived xenograft (PDX) model of squamous cell lung cancer. Our results demonstrated that CTGF inhibition enhances the effects of gemcitabine chemotherapy in PDX model of squamous cell lung carcinoma. These results clearly suggested that CTGF has a profound effect on lung tumorigenesis, as its inhibition not only causes attenuation in tumor growth but also potentiates the chemotherapeutic sensitivity of commonly used drugs for NSCLC. We have also elucidated that tumor hypoxia and Yap signaling are responsible for CTGF up-regulation in lung carcinoma. Overall, our study underscores the significance of CTGF inhibition in non-small cell lung carcinoma and offers the potential use of FG-3019 for its treatment. Citation Format: Priyanka Chaudhary, Marie-Liesse Labat, Guangfang Wang, Mark Onaitis. Connective tissue growth factor: Novel therapeutic target for non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3047." @default.
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• W2956124859 date "2019-07-01" @default.
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• W2956124859 title "Abstract 3047: Connective tissue growth factor: Novel therapeutic target for non-small cell lung cancer" @default.
• W2956124859 doi "https://doi.org/10.1158/1538-7445.am2019-3047" @default.
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