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  • American Association for Cancer Research (AACR)  (8)
  • Park, Young Soo  (8)
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  • American Association for Cancer Research (AACR)  (8)
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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 1058-1058
    Abstract: BACKGROUND: The gastrointestinal stromal tumor (GIST) has activating mutations in either KIT or platelet-derived growth factor receptor alpha (PDGFRa) gene, and tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib and regorafenib remain the mainstay of anti-GIST treatment. Patient-derived xenografts (PDXs) are useful preclinical models in cancer research, owing to their demonstration of more real tumor heterogeneity and complexity, compared with cell lines and cell line-based xenograft models. PDX models have been established using numerous tumor types, however, there are only a few PDX models of GIST because of its very low success rate. As we have been establishing PDXs from GIST patients since 2012, in this study, we report the established PDXs and the clinopathological characteristics related to the successful establishment of GIST PDXs. MATERIALS and METHODS: PDXs have been established in NOD-scid Il2rg-/- (NSG) mice by implanting GIST tumor fragments from 185 patients who underwent surgical resection prior to and after tyrosine kinase inhibitors from July, 2012 to July, 2017. The established PDXs passaged greater than F2 generation. Chi-square test and logistic regression were used for comparison. RESULTS: Of a total of 185 patients, 66 (35.7%) patients were TKI-naïve, 21 (11.4%) had residual disease after control with TKIs, and the remaining 98 (53.0%) showed disease progression after TKIs at the time of surgical resection. The success rate of establishment of GIST PDXs was 16.8% (31/185). In univariate analyses, a higher engraftment rate was observed for tumors derived from patients with disease progression after TKIs (TKI-naïve vs residual disease vs progressive disease; p & lt;0.001), larger tumor size (≤50 mm vs 50-100 mm vs & gt;100 mm; p & lt;0.001), more mitotic count (≤10/50 HPFs vs & gt;10/50 HPFs; p & lt;0.001), higher Ki-67 index ( & lt;1/3 vs ≥1/3; p & lt;0.001), higher cellularity (low vs high; p & lt;0.001), or tumor necrosis (absence vs presence; p=0.001). In addition, PDX engraftment success rate was higher with tumors harboring primary mutation in KIT exon11 (vs other mutations; p=0.025) or with metastatic tumor lesions (vs primary site; p & lt;0.001). In multivariate analysis including significant factors in the univariate analyses, Ki-67 index (p=0.001) and largest tumor size (p=0.058) were independent factors for success of PDX establishment. CONCLUSION: Clinicopathologic factors such as disease progression after TKIs, larger tumor size, more mitotic count, higher Ki-67 index, higher cellularity or tumor necrosis were associated with higher success rate of PDX establishment. Especially, largest tumor size and Ki-67 index were independent factors for successful PDX engraftment. These findings will be helpful to establish PDX models more efficiently in GIST. Citation Format: Young-Soon Na, Min-Hee Ryu, Young Soo Park, Chae-Won Lee, Ju-Kyung Lee, Yangsoon Park, Jung Min Park, Jungeun Ma, Yoon-Koo Kang. Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: Analyses of clinopathological characteristics related with success [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 1058.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 1269-1269
    Abstract: BACKGROUND: KIT-targeting tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib and regorafenib are the standard treatment for patients with gastrointestinal stromal tumor (GIST). However, most patients eventually develop treatment resistance to these standard therapies, and new agents must be introduced upon disease progression. Before TKIs were available, most of the conventional cytotoxic agents did not show sufficient clinical activity in GIST patients. However, a recent preclinical study demonstrated that 37 of the 89 FDA-approved anti-tumor drugs including paclitaxel (PTX) possess antitumor effect in at least one GIST cell line. Therefore, in this study, we aimed to evaluate the efficacy of PTX as a salvage treatment for GIST patients who exhibited treatment failure after standard TKI therapy using in-vitro/vivo models. MATERIALS and METHODS: The effect of PTX in GIST was examined by cell viability assay and rhodamine 123 (Rho123) efflux assay using GIST cells including established patient-derived GIST cell lines, and in animal models with patient-derived xenografts (PDXs) established from patients with GIST tumors refractory to TKIs. Multidrug resistance 1 (MDR1) mRNA expression by reverse transcription-PCR (RT-PCR) and P-glycoprotein (Pgp) expression by Western blotting or immunohistochemistry were evaluated in 20 patients’ tumor tissues, 9 GIST cell lines and 21 PDXs. To investigate the role of Pgp on PTX treatment, a stable MDR1-expressing GIST T1 cell line (GIST-T1-ABCB1#17) was prepared and compared with parent GIST T1 cell line. Verapamil was used as a Pgp inhibitor. RESULTS: Compared to imatinib-sensitive GIST-T1 harboring KIT exon 11 mutation and imatinib-resistant GIST-T1/816 harboring KIT exon 11 and 17 mutations, the patient-derived imatinib- and sunitinib-resistant GIST-R3 cell line harboring KIT exon 11 and 17 mutations was more resistant to PTX. Higher Rho123 efflux was observed in GIST-R3 which had high Pgp expression than in GIST-T1 and GIST-T1/816 which had low Pgp expression. The tumor growth inhibition of PTX was greater in xenografts with low Pgp expression (GIST-T1/816 xenografts and GIST-RX10 PDXs) than in xenografts with high Pgp expression (GIST-R3 xenografts and GIST-RX4 PDX). The GIST-T1-ABCB1#17, a stable MDR1-expressing GIST T1 cell line, exhibited a higher Pgp activity and a less sensitivity to PTX than the parent GIST-T1 cell line. The resistance of GIST-T1-ABCB1#17 to PTX was overcome by verapamil. CONCLUSION: Pgp expression was an important mechanism of resistance to PTX in preclinical GIST models. PTX is worth being tried clinically as a salvage treatment in patients with refractory GISTs with low Pgp expression. Citation Format: Young-Soon Na, Min-Hee Ryu, Young Soo Park, Chae-Won Lee, Ju-Kyung Lee, Jung Min Park, Yangsoon Park, Yoon-Koo Kang. P-glycoprotein expression in refractory gastrointestinal stromal tumors and its implication in the efficacy of paclitaxel as a salvage treatment [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 1269.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 3
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 12, No. 11_Supplement ( 2013-11-01), p. B211-B211
    Abstract: Background: Fibroblast growth factor receptor 2 (FGFR2) amplification is associated with tumorigenesis of gastric cancer and can be a promising molecular target for the treatment of FGFR2-amplified gastric cancer. So far, the most optimal single method to screen patients with FGFR2 amplification has not been determined. To screen patients with gastric cancer harboring FGFR2 amplification, we aim to investigate whether qPCR can replace the FISH method which is the golden standard but less sensitive and much more expensive than qPCR. Methods: FISH (Abnova, #FG0018) and qPCR (Applied Biosystems, HS05182482_cn) method for FGFR2 amplification were performed with formalin-fixed paraffin-embedded (FFPE) tissues of patients with gastric cancer who were diagnosed from 2007 to 2012 in Asan Medical Center, Seoul, Korea, and whose FFPE tissues contained at least 70% of tumor cells. qPCR was conducted initially in 26 patients who had both endoscopic biopsy and surgical tissues in the diagnosis to figure out which samples are better between biopsy and surgical tissues. According to the results, 182 patients with endoscopic biopsy tissues were further included. FISH was defined as positive in case of FGFR2 to CEP10 ratio & gt; 2.0. Results: In 26 patients who had paired endoscopic biopsy and surgical samples, the qPCR-based copy number assay for FGFR2 amplification was more sensitive in biopsy samples; i.e., FGFR2 copy number by qPCR was higher in biopsy samples in 13 (50%) patients, while it was higher in surgical samples only in 3 (11.5%) patients. In a total of 208 endoscopic biopsy FFPE samples including 182 patients with biopsy tissues, copy number of FGFR2 ranged from 0.8 to 399.0 (median 15.9) by qPCR and from 0.7 to 166.9 (median 6.1) by FISH. 16 biopsy samples showing FGFR2 copy number & gt; 10 by qPCR were all FISH-positive, while 192 biopsy samples showing FGFR2 copy number & lt; 10 by qPCR were all FISH-negative. In cases of FGFR2 copy number & gt; 10 in biopsy tissues by qPCR, the copy numbers were very well correlated between qPCR and FISH in all patients, and were also over 10 in surgical tissues regardless of methods in 26 patients. The positive rate of FGFR2 amplification was 7.7% with a cut-off value of 10 by qPCR. Conclusion: This study suggests that it is better to use biopsy samples than surgical tissues to detect FGFR2 amplification by qPCR; and for patient screening in gastric cancer, the optimal cut-off value for definite FGFR2 amplification by qPCR is 10 in comparison with the results of FISH. Clinical relevance of intermediate FGFR2 copy number elevation & lt; 10 by qPCR needs to be addressed in future clinical trials using FGFR2 inhibitors. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B211. Citation Format: Young-Soon Na, Young Soo Park, Min-Hee Ryu, Chae-Won Lee, Hye Jin Park, Ju-Kyung Lee, Sook Ryun Park, Baek-Yeol Ryoo, Yoon-Koo Kang. Comparison of detection of FGFR2 amplification by quantitative real-time-PCR (qPCR) and fluorescent in situ hybridization (FISH) in gastric cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B211.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 4
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 6, No. 4 ( 2013-04-01), p. 349-359
    Abstract: Helicobacter pylori (H. pylori) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with H. pylori. 15-PGDH expression in gastric biopsies from H. pylori–infected (n = 25) and noninfected (n = 15) subjects was analyzed by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. 15-PGDH DNA methylation was evaluated by methylation-specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, extracellular signal–regulated kinase (ERK)1/2, TLR4, and MyD88 in response to H. pylori infection was assessed by immunoblot analysis. Compared with negative specimens, H. pylori–positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four H. pylori–infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by H. pylori eradication therapy. In parallel with suppressing 15-PGDH expression, H. pylori infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of EGF receptor (EGFR)-Snail. Inhibition of Snail and MyD88 reversed suppression of 15-PGDH expression, and siMyD88 reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 and EGFR inhibitor also restored 15-PGDH expression. H. pylori appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 or EGFR-Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in H. pylori–induced gastric carcinogenesis. Cancer Prev Res; 6(4); 349–59. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1808-1808
    Abstract: Gastric cancer (GC) is the most common cancer type in Asia. Surgical resection and chemotherapy is standard treatment of GC. Molecular therapeutic targets and mechanism contributing to develop the gastric cancer is poorly understood. To discover the molecular target in gastric cancer, we analyzed gene expression data from gastric cancer patients. Data analysis reveals that nuclear receptor ESRRG is top candidate gene conferring the tumor suppressive property in gastric cancer. ESRRG expression is down-modulated by Helicobacter pylori (H. pylori) infection, which is one of causing factor triggering gastric cancer. In addition, ectopically over-expressed ESRRG protects the cell from H. pylori infection and suppressed cancer cell growth in vitro and in vivo mouse model. Gene expression profile reveals that TFF1, which is well known as tumor suppressor in gastric cancer is down-stream target of ESRRG and ESRRG well reflects clinical outcome in gastric cancer. Our study provides new molecular insights how ESRRG regulates gastric cancer cell growth induced by H. pylori and suggests possibility that ESSRRG can be therapeutic target for the treatment of gastric cancer patients. Citation Format: Myoung-Hee Kang, Yong-Soo Lee, Jin-Hak Jung, Young Soo Park, Jin-Yong Jeong, Mi-Na Kweon, Chan-Ki Paik, Seung-Jae Myung, Yun-Yong Park. Nuclear receptor, ESRRG functions as tumor suppressor by preventing Helicobacter pylori infection in gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1808.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 6
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    Online Resource
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3986-3986
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3986-3986
    Abstract: Introduction: With the recent introduction of human epidermal growth factor receptor 2 (HER2) targeted therapies for patients with advanced gastric cancer (AGC), determining HER2 status is essential to select the patients who may benefit from this treatment. The current standard method assessing HER2 positivity is immunohistochemistry (IHC) or in situ hybridization assays, but this way of HER2 assessment has weaknesses especially when considering tumor heterogeneity. Using digital droplet polymerase chain reaction (ddPCR) technique, we evaluated HER2 amplification in both tissue and plasma samples collected from AGC patients and analyzed clinical implication of HER2 amplification in circulating tumor DNA. Method: Biopsied tissue and plasma samples were collected from patients with metastatic or recurrent AGC who were enrolled in AGC biomarker study conducted at Asan Medical Center. Samples were obtained before the start of anti-cancer treatment. HER2 amplification in DNA from tissue and cell-free DNA from plasma were determined by ddPCR, performed in Kindai University. Results: Samples of 63 patients with HER2 positive GC and 37 patients with HER2 negative GC enrolled between April 2014 and October 2017 were included in the analysis. As expected, the median HER2 copy number (CN) was higher in patients diagnosed as HER2 positive than negative, both for tissue (4.54 vs 0.95, P & lt; 0.001) and plasma (1.49 vs 1.07, P & lt; 0.001). ROC curve analysis showed 83.8% specificity and 69.8% sensitivity for tissue HER2 positivity at 1.17 CN of plasma HER2. In patients receiving anti-HER2 therapy (n=57), there was a trend for worse progression-free survival (PFS) outcome in patients with higher plasma HER2 CN ( & gt;1.5 vs ≤1.5), although no statistical significance was seen (median PFS 6.67 vs 8.19 months, P = 0.172). In multivariate Cox regression analysis including the age ( & gt;60 vs ≤60), HER2 IHC intensities (2+ vs 3+), and risk groups determined by Koo et al.’s prognostic model (Good vs Moderate vs Poor), higher plasma HER2 CN ( & gt;1.5 vs ≤1.5) was significantly associated with poor PFS (HR 2.22, 95% CI 1.14-4.32, P = 0.019). However, when tumor burden (sum of largest diameter of all measurable lesions) was combined as another factor in patients with measurable disease (n=39), plasma HER2 CN was no longer an independent factor (HR 1.38, 95% CI 0.58-3.27, P = 0.466) and larger tumor burden ( & gt;6.5cm vs ≤6.5cm) was found to be an independent prognostic factor for poor PFS (HR 2.63, 95% CI 1.12-6.21, P = 0.027), instead. Of note, plasma HER2 CN showed a positive relationship with tumor burden multiplied by tissue HER2 CN in linear regression (β=0.32, P = 0.002). Conclusion: Using the ddPCR technique, we found that plasma HER2 CN was significantly increased in HER2 positive GC patients compared to negative patients. However, plasma HER2 CN did not provide more information on predicting therapeutic effects than the tumor burden in patients receiving anti-HER2 therapy. Citation Format: Kyoungmin Lee, Kazuko Sakai, Min-Hee Ryu, Jae-Joon Kim, Young Soo Park, Young-Soon Na, Jungeun Ma, Hana Na, Kazuto Nishio, Yoon-Koo Kang. Digital droplet PCR measurement for plasma HER2 amplification in patients with AGC [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 3986.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2874-2874
    Abstract: Background: The intratumoral heterogeneity of HER2 expression in gastric cancer (GC) is a major challenge when identifying patients who will benefit from HER2-targeting therapy. The aim of this study is to evaluate the significance of re-evaluation of the HER2 status by repeat endoscopic biopsy in GC patients with an initial, HER2-negative endoscopic biopsy. Methods: Patients with unresectable or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma and who will receive first-line chemotherapy, were eligible if the HER2 was negative on the initial endoscopic biopsy. HER2 positivity was defined as immunohistochemistry (IHC) 3+ or IHC 2+/fluorescence in situ hybridization (FISH) + using the GC scoring system. A repeat endoscopic biopsy was performed in ≥6 different primary tumor sites immediately after obtaining initial HER2-negative results. Results: From May 2011 to April 2013, a total of 183 eligible patients were enrolled. Baseline characteristics at the time of the initial biopsy were as follows: tumor location, GEJ∼fundus/body/antrum/diffuse stomach=22(12.0%)/47(25.7%)/68(37.2%)/46(25.1%); Lauren classification, intestinal/diffuse/mixed=53(29.0%)/111(60.7%)/19(10.4%); and HER2 IHC score, 0/1/2=149(81.4%)/26(14.2%)/8(4.4%). The median number of biopsy pieces per patient was 5 (range, 1-15) and 10 (range, 1-15) on the initial and repeat biopsy, respectively (P & lt;0.0001). There was no difference in the median ratio of the number of cancer-containing pieces/total pieces; 0.86 (range, 0.13-1) vs. 0.89 (range, 0.10-1) (P=0.679). As the repeat biopsy identified 16 patients with HER2-positive tumor, the rate of rescued HER2 positivity was 8.7% (95% CI 4.6-12.8%). Rescued HER2 positivity was associated with tumor location (diffuse stomach vs. others=0% vs. 11.7%, P=0.013), Bormann type (IV vs. others=0% vs. 11.7%, P=0.013), and the HER2 IHC score on the initial biopsy (0 vs. 1 vs. 2 = 6.7% vs. 15.4% vs. 25.0%, P=0.028). In multivariate analysis, the HER2 IHC score (1/2 vs. 0, odds ratio=3.78; P=0.016) was an independent predictive factor for rescued HER2 positivity. Conclusions: Repeat endoscopic biopsy is recommended in order to check the HER2 status again even if the initial endoscopic biopsy is HER2 negative in metastatic or unresectable GC. Note: This abstract was not presented at the meeting. Citation Format: Sook Ryun Park, Young Soo Park, Baek-Yeol Ryoo, Chang Gok Woo, Hwoon-Yong Jung, Jeong Hoon Lee, Gin Hyug Lee, Min-Hee Ryu, Yoon-Koo Kang. A prospective study of a repeat endoscopic biopsy to identify HER2-positive tumors following an initial HER2-negative endoscopic biopsy in unresectable or metastatic gastric cancer patients: GASTHER1 study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2874. doi:10.1158/1538-7445.AM2014-2874
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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  • 8
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    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4755-4755
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4755-4755
    Abstract: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have significantly improved on clinical outcomes in many non-small cell lung cancer (NSCLC) patients. However, therapeutic efficacy of EGFR TKIs is limited on patients who have gefitinib-sensitizing EGFR gene mutations (Exon 19del, L858R). Although, not as sensitive as patients who have these mutations, some patients who have wild type EGFR responded to EGFR TKIs. Therefore, we hypothesized that there are underlying mechanisms that cause most of wild type EGFR NSCLC patients to be refractory. In this study, we demonstrated that intractability of EGFR TKIs in wild type EGFR NSCLC was closely related to clathrin mediated endocytosis (CME), which offered a novel strategy for overcoming EGFR TKI resistance. At first, we classified wild type EGFR NSCLC cell lines into gefitinib sensitive cells and refractory cells according to the IC50 values of gefitinib. Then, we performed immunocytochemistry (ICC) and immunoprecipitation (IP) to examine EGFR levels in early endosome with gefitinib treatment in gefitinib sensitive and refractory cell lines. As a result, EGFR endocytosis proceeded in gefitinib refractory cell lines (SNU1327, H1703) despite of gefitinib treatment, but not in sensitive cell lines (H358, Calu-3). EGFR is known to be internalized through CME and non clathrin mediated pathway (NCE). Then, we treated CME inhibitor, Phenylarsine oxide (PAO), or NCE inhibitor, Filipin III, in gefitinib sensitive and refractory cell lines to vefity if there is any difference in dependency of two main endocytosis pathway. As the ICC and IP data shown, blocking NCE did not inhibit EGFR internalization but blocking CME inhibited EGFR endocytosis in gefitinib refractory cell lines. Interestingly, it was the opposite in the gefitinib sensitive cell lines. Furthermore, we observed that cell survival decreased significantly during CME inhibition and combination treatment with gefitinib in refractory cell lines, but not in sensitive cell lines. To enlighten the elusive pathway, we examined the ratio of EGFR recycling and degradation. As a result, we observed EGFR degradation during CME or NCE proceeded conditions in gefitinib sensitive cell lines. However, in gefitinib refractory cell lines, EGFR protein was accumulated in CME dependent manner. These results implied that CME led EGFR recycling and sustained gefitinib refractory cell lines. For further studies, we are confirming signal molecules activated through CME. In conclusion, our study provides the possibility of new scheme that clathrin-mediated endocytosis inhibition could be a potential therapeutic strategy for the limitation of EGFR TKI therapy. This study was supported by a Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A2057538). Citation Format: Boyeon Kim, Young Soo Park, Jae Sook Sung, Jong Won Lee, Saet Byeol Lee, Yeul Hong Kim. Clathrin mediated endocytosis as a potential therapeutic strategy for overcoming refractoriness of EGFR TKI [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 4755.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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