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  • American Association for Cancer Research (AACR)  (13)
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  • American Association for Cancer Research (AACR)  (13)
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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2669-2669
    Abstract: As the representative targeted anticancer drug for colon cancer patients, Erbitux is the EGFR targeted therapeutic antibody and used for treatment of KRAS wild-type colon cancer patients. Even some patients with KRas wt gene did not respond to Erbitux. However, there is no treatment available for Erbitux-resistant patient group with KRAS WT gene, which is almost 50% of KRAS WT gene holders. Recently, our team identified Erbitux primary resistant related proteins named as CRG (Cetuximab-Resistant Gene) by array analysis based Erbitux responder or nonresponder colon cancer patients derived tissues and confirmed by in vitro and in vivo assay system. Based on these results, we synthesized a novel series of CRG targeted inhibitor. CRG inhibitor (CRG i;WM compound) is a lead compound for treating colon cancer patients who do not respond to Erbitux and have KRAS wild-type gene. CRG i has potent in vitro enzyme activity and high anticancer activity against various colon cancer cell lines with good selectivity in in vitro and in vivo system. Furthermore, the compound has good potent ADME/Tox. profiles for optimized lead. CRG i also displays strong anticancer effect in in vivo xenograft models and patient-derived xenograft (PDX) models. In addition, CRG i shows promising signs of overcoming Erbitux resistance in CRG knockout cells-derived xenograft model. We continue to discover improved preclinical candidates with better selectivity and ADME/Tox. profiles and validate predictive biomarker in colon cancer patients. In these efforts, we found some compounds with better profiles than CRG i. We are also trying to develop small molecules having highly potent activity against mutant CRG. In conclusion, active CRG is a promising biomarker and target for Erbitux-resistant KRAS wt colon cancer patients. Our compounds can be promising therapeutic agents for Erbitux-resistant KRAS wt colon cancer patients. Citation Format: Chun-Ho Park, Sun-Chul Hur, Joseph Kim, Dae Hee Lee, Yoon Sun Park, Jae-Sik Shin, Seung-Woo Hong, Jai-Hee Moon, Hyojin Kim, So Hee Lee, Hyebin Park, Joonyee Jung, Mi Jin Kim, Sang Soo Park, Jun Ki Hong, Ji Hee Gong, Jieun Kim, Il-Whea Ku, Hyun Ho Lee, Dong-Hoon Jin. Identification of a novel small-molecule inhibitor for treatment of human colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2669.
    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: 2018
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2909-2909
    Abstract: Lung cancer is second most common cancer in the world. Non Small Cell Lung Cancer (NSCLC) accounts approximately 80-85% of all lung cancer diagnosis. Traditional therapies of this disease were surgical resection, chemotherapy, and radiotherapy, alone or in combination. In addition, targeted therapeutic approach was based on the concept of discovering genetic alterations and the signaling pathways in cancer. Recently, to overcome the critical points for standard therapies, many groups were studied immunotherapeutic approaches, such as programed cell-death protein 1 (PD-1) antibody. However, rational use of these agents has been limited by the lack of a definitive predictive biomarker. Therefore, we identified new target, cancer immunotherapy related gene, CMG by shRNA libraries screening analysis on chemo-agents & target therapy resistant non-small cell lung cancer cells. First of all, we investigated CMG expression by immunohistochemistry in various tissue microarray (TMA). These results show that CMG highly expressed in Lung cancer, Liver cancer, and gastric cancer. We investigated target potentials on lung cancer, liver cancer, and gastric cancer cell lines using in vitro and in vivo assay system. Knockdown of CMG by CMG shRNA was induced cell death in various cancer cell lines. In addition, suppression of CMG was induced tumor size regression in CMG shRNA stable cell lines-derived xenograft model. Based on these results, we synthesized a novel series of CMG therapeutic antibody. CMG therapeutic antibody is a lead antibody for treating Lung cancer patients who express CMG gene. These antibodies have anti-cancer effects and immunotherapeutic effects in lung cancer (NSCLC), liver cancer, and gastric cancer. In addition, the in vivo efficacy of CMG antibody was assessed in mouse lung cancer derived syngeneic mouse model. The CMG antibody was tri-daily i.p. injected and the tumor volume was measured and compared between groups. Dramatic tumor regression was observed in CMG antibody treated group. These results were shown that these antibodies have immunotherapeutic potentials. In conclusion, CMG is a promising target for Lung cancer patients (chemo-agents resistant or PD-1 resistant Lung cancer patienrts). Our antibodies can be promising therapeutic agents for lung cancer, Liver cancer, and gastric cancer. Citation Format: Jai-hee Moon, Dae Hee Lee, Jae-Sik Shin, Joseph Kim, Yoon Sun Park, Seung-Woo Hong, So Hee Lee, Mi Jin Kim, Joonyee Jung, Chun-Ho Park, Sun-Chul Hur, Hyojin Kim, Hyebin Park, Sang Soo Park, Jun Ki Hong, Ji Hee Gong, Jieun Kim, Hyun Ho Lee, Il-Whea Ku, Dong-Hoon Jin. Development of new mechanism based therapeutic antibodies in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2909.
    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: 2018
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  • 3
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 23 ( 2015-12-01), p. 5391-5403
    Abstract: Purpose: Previous study identified E2F1 as a key mediator of non–muscle-invasive bladder cancer (NMIBC) progression. The aim of this study was to identify the E2F1-related genes associated with poor prognosis and aggressive characteristics of bladder cancer. Experimental Design: Microarray analysis was performed to find E2F1-related genes associated with tumor progression and aggressiveness in the gene expression data from 165 primary patients with bladder cancer. The biologic activity of E2F1-related genes in tumor progression and aggressiveness was confirmed with experimental assays using bladder cancer cells and tumor xenograft assay. Results: The expression of E2F1 was significantly associated with EZH2 and SUZ12. The overexpression of E2F1, EZH2, and SUZ12 enhanced cancer progression including cell colony formation, migration, and invasiveness. Knockdown of these genes reduced motility, blocked invasion, and decreased tumor size in vivo. E2F1 bound the proximal EZH2 and SUZ12 promoter to activate transcription, suggesting that E2F1 and its downstream effectors, EZH2 and SUZ12, could be important mediators for the cancer progression. In addition, we confirmed an association between these genes and aggressive characteristics. Interestingly, the treatment of anticancer drugs to the cells overexpressing E2F1, EZH2, and SUZ12 induced the expression of CD44, KLF4, OCT4, and ABCG2 known as cancer stem cell (CSC)–related genes. Conclusions: The link between E2F1, EZH2, and/or SUZ12 revealed that E2f1 directly regulates transcription of the EZH2 and SUZ12 genes. The signature of E2F1–EZH2–SUZ12 shows a predictive value for prognosis in bladder tumors and the E2F1–EZH2–SUZ12–driven transcriptional events may regulate the cancer aggressiveness and chemo-resistance, which may provide opportunity for development of new treatment modalities. Clin Cancer Res; 21(23); 5391–403. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 395-395
    Abstract: The main cause of death for colorectal cancer (CRC) patients is the development of metastatic lesions at sites distant from the primary tumor. Therefore, it is important to find biomarkers that are related to the metastasis and to study the possible mechanism. Recent data have shown that soluble attractant molecules called chemokines support the metastasis of certain cancers to certain organs. To identify molecular regulators that are differentially expressed in liver metastasis of CRC, PCR array was performed and CCL7 showed remarkable overexpression in liver metastatic tumor tissues. To validate the result of PCR array, 30 patients with primary CRC and liver metastases were selected. Immunohistochemistry and real-time PCR analysis showed that CCL7 was expressed in normal colonic epithelium and the expression was higher in liver metastases than in primary CRC. CCR1, CCR2, and CCR3, receptors of CCL7, were not expressed in normal colonic epithelium nor colon and metastatic cancer, but expressed in normal hepatocytes and stroma by immunohistochemical staining. Real-time PCR showed that the expressions of CCR1, CCR2, and CCR3 were also higher in liver metastases than in primary CRC. There would be chemokine/chemokine receptors interactions between CCL7 and its receptors in liver, which supply the environment for metastatic colon cancer cells to survive and proliferate in liver. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 395. doi:10.1158/1538-7445.AM2011-395
    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: 2011
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  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P1-08-23-P1-08-23
    Abstract: Background: Androgen receptors (AR) has emerged as a prognostic factor predicting survival and recurrence in breast cancer. However, the role of AR as a predictor of pathological complete response (pCR) rate after neoadjuvant chemotherapy by subtypes is unclear. This study aimed to investigate according to AR in breast cancer patients undergoing neoadjuvant chemotherapy as a predictor. Furthermore, we estimated the relationship between AR expression and clinicopathological factors. Method: We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center from April 2016 to October 2019. We retrospectively collected the medial records that the clinicopathologic information and AR expression analyzed according to cancer stage, hormonal receptor status, HER2 status, tumor subtype, pCR. Results: Among the 624 breast cancer patients, 529 (84.8%) were AR positive patients and 95 (15.2%) were AR negative patients. The mean age of the patients was 50.0 years. The rate of pCR was 31.4% (196/624). AR negative patients had significantly high rate of pCR than AR positive patients. (AR (-) 43.2% vs. AR (+) 29.3%, p = 0.0074). AR positive patients showed more ER positivity, PR positivity, HER2 positivity and luminal A subtype. A higher proportion of AR positive patients compared to AR negative patients received target therapy and hormonal therapy (target therapy, AR (-) 15.8% vs. AR (+) 43.9%, hormonal therapy, 14.7% vs. 71.0%, p & lt;.0001). The tumor factors associated with pCR were early stage, histologic grade 3, ER negativity, PR negativity, AR positivity, HER2 positivity, and high ki-67%. According to subtypes of tumor, the correlation between AR expression and pCR was. significantly higher in AR negative luminal A type (AR (-) 28.57% vs. AR (+) 7.26%, p =0.0215). The other subtypes did not show a statistically significant difference. Conclusion: This study shows that AR expression is predominant in luminal A subtype. When determining neoadjuvant chemotherapy in luminal A subtype, AR expression can be considered as a pCR predictive marker. Citation Format: Eun-Gyeong Lee, Dong-Eun Lee, Jai Hong Han, Seeyoun Lee, Han-Sung Kang, Eun Sook Lee, Youngmee Kwon, Hyun Hee Kim, Hee Jung Chae, Sung Hoon Sim, Keun Seok Lee, So-Youn Jung. Androgen receptor as predictive marker for pathologic complete response in breast cancer with neoadjuvant chemotherapy [abstract] . In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-23.
    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: 2022
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 6038-6038
    Abstract: Purpose: Patient-derived organoid (PDO) is emerging tool for drug sensitivity evaluation. Organoid technology has revolutionized the study of human organ development, disease and therapy response tailored to the individual. Therefore, we set up conditions for breast cancer PDOs and establish an in vitro drug evaluation system for future therapeutic approaches. Methods: All specimens were collected from histologically confirmed breast cancer patients after obtaining IRB approval from the National Cancer Center (NCC2017-0146, NCC2020-0299) under patient’s informed consent. Fifty-four patient samples obtained from surgery or biopsy were delivered to the laboratory within 1-2 hours for organoid establishment. All process for cell isolation from human tissues, criteria of successful culture and passaging, quality control (QC), producing genomic and histologic data were adjusted to make standard operating procedure. For long-term cultured PDOs, we tested 30 drugs including kinase inhibitor or standard therapeutic drugs with concentration from 0.001uM to 100uM using 384well plate and the results were analyzed with AUC data with bortezomib as a control. Results: We optimized organoids culture conditions for breast cancer tissues. Total of 54 tissues included disease subtypes as following: hormone positive (n=32), HER2 positive (n=2), triple-negative (n=19), and other (n=1). Nine organoids were successfully long term cultured over 5 passages and 4 were successfully cryopreserved. Clinic characteristics (TNM stages, subtypes, and disease status) showed no significant association with success of organoid establishment. Also, we confirmed that organoids had similar characteristics to the patients tissue through histological data (H & E, ER, PR, HER2, Ki-67, and CK-19). Measurement of AUC values for tested drugs showed variety range which implicates different drug sensitivity of each organoid. Currently, genetic information of long-term cultured organoid is ongoing with comparative analysis of drug sensitivity. Conclusions: We have established breast cancer organoids which reflect molecular characteristics of the original tumor. This model will serve as the system that can recapitulate drug response profiles of human cancer, and pave the way for screening innovative drugs, identifying novel targets, and stratifying patients for pertinent therapeutic options. (This work was supported by National Cancer Center, Korea (No.2010120) and National Research Foundation of Korea grant, funded by the Korea government (MSIT) (No. 2020M3A9A5036362)) Citation Format: Hyunjin Kim, So-Youn Jung, Sung Hoon Sim, Hee Jung Chae, Yun-Hee Kim, Yena Kim, Eun Gyeoung Lee, Seeyoun Lee, Jai Hong Han, Young Mi Kwon, Eun Sook Lee, Keun Seok Lee, Sun-Young Kong. Target therapeutics evaluation using patient-derived organoids from breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6038.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS7-62-PS7-62
    Abstract: BACKGROUND The incidence of breast cancer is increasing in Korea. Breast cancer in young Korean women ( & lt; 40 years) is rare, but the rate of young age breast cancer incidence in Korea is higher than that in western countries. This study was aimed to evaluate the tumor characteristics of young age breast cancer patients ( & lt; 40 years) among Korean women. METHODS Among the Korean women, who were diagnosed with breast cancer from 2010 to 2015, we identified 10,897 cases of nationally representative sample data. The data was made through 10% systematic sampling of the Korea Central Cancer Registry (KCCR). We conducted a chart review survey to collect the data about tumor size, regional lymph node status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status according to the Collaborative Stage version 2 (CSv2) Data Collection System. We described the number and percentage of the breast cancer stage distribution, tumor grade and intrinsic subtypes by the patient age groups ( & lt; 40 years, 40-49 years, 50-59 years, and ≥ 60 years), and evaluated the tumor characteristics in young age breast cancer patients ( & lt; 40 years). RESULTS The number of young age breast cancer patients was 1,245 (11.4% of & lt; 40 years vs 35.4% of 40~49 years vs 30.8% of 50~59 years vs 22.4% of ≥ 60 years; P & lt;.001). Young age breast cancer patients were more likely to be diagnosed with larger tumors (T2: 41.6% vs 36.4% vs 36.5% vs 38.4%; T3: 10.1% vs 7.3% vs 6.5% vs 6.2 %; P & lt;.0001), more positive lymph node status (41.2% vs 32.7% vs 35.7% vs 32.5%; P & lt;.0001), and higher tumor grade (grade 3, 26.8% vs 19.4% vs 23.5% vs 22.1%; P & lt;.0001). According to intrinsic subtypes using ER, PR, and HER2, triple negative subtype was found more in young age breast cancer (18.2% vs 11.0% vs 12.2% vs 13.5%; P & lt;.0001). CONCLUSION This study shows that young age breast cancer patients ( & lt; 40 years) in Korea have more aggressive tumor including advanced cancer stage at diagnosis, higher tumor grade, and triple negative intrinsic subtype. Therefore, we need to identify high risk group for young age breast cancer ( & lt; 40 years) and support their active surveillance. These findings using national cohort provide important information for establishing a national strategy of cancer care to manage young age breast cancer patients. Citation Format: Junyup Kim, So-Youn Jung, Eun-Gyeong Lee, Eun Sook Lee, Han-Sung Kang, See Youn Lee, Jai Hong Han, Heein Jo, Hyun hee Kim, Young-Joo Won, Seri Hong, Jae Jun Lee. Tumor characteristics of young age breast cancer patients using a nationally representative sample of the Korea central cancer registry (KCCR) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-62.
    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: 2021
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 4 ( 2016-02-15), p. 855-865
    Abstract: The generation of reactive oxygen species (ROS) is required for proper cell signaling, but must be tightly regulated to minimize deleterious oxidizing effects. Activation of the NADPH oxidases (Nox) triggers ROS production and, thus, regulatory mechanisms exist to properly control Nox activity. In this study, we report a novel mechanism in which Nox1 activity is regulated through the proteasomal degradation of Nox organizer 1 (NoxO1). We found that through the interaction between NoxO1 and growth receptor–bound protein 2 (Grb2), the Casitas B–lineage lymphoma (Cbl) E3 ligase was recruited, leading to decreased NoxO1 stability and a subsequent reduction in ROS generation upon epidermal growth factor (EGF) stimulation. Additionally, we show that EGF-mediated phosphorylation of NoxO1 induced its release from Grb2 and facilitated its association with Nox activator 1 (NoxA1) to stimulate ROS production. Consistently, overexpression of Grb2 resulted in decreased Nox1 activity, whereas knockdown of Grb2 led to increased Nox1 activity in response to EGF. CRISPR/Cas9-mediated NoxO1 knockout in human colon cancer cells abrogated anchorage-independent growth on soft agar and tumor-forming ability in athymic nude mice. Moreover, the expression and stability of NoxO1 were significantly increased in human colon cancer tissues compared with normal colon. Taken together, these results support a model whereby Nox1 activity and ROS generation are regulated by Grb2/Cbl-mediated proteolysis of NoxO1 in response to EGF, providing new insight into the processes by which excessive ROS production may promote oncogenic signaling to drive colorectal tumorigenesis. Cancer Res; 76(4); 855–65. ©2016 AACR.
    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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  • 9
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4790-4790
    Abstract: EGFR mutated lung cancer shows approximately 10-15% of non-small cell lung cancer (NSCLC). Although the best therapeutic EGFR tyrosine kinase inhibitors (TKIs) targeting mutant EGFR, such as gefitinib and erlotinib, are used in the first line treatment of patients with advanced EGFR mutated NSCLC, the acquired resistance to the drugs usually appears in 10-12 months of therapy by the occurrence of a second EGFR mutation T790M. YH25448, a highly mutant-selective and irreversible 3rd generation EGFR TKI potently penetrating blood-brain barrier (BBB) penetration, targets both activating EGFR mutations Del19, L858R and T790M mutation while sparing wild type. In NSCLC cell lines and primary cancer cells from patients harboring EGFR mutations, YH25448 showed more potent inhibition of cancer cell growth and significantly increased tumor cell apoptosis compared to osimertinibs, which is one of 3rd generation EGFR TKIs. In vivo mouse model implanted with H1975 cells, YH25448 treatment at the once-daily showed a dramatic dose-dependent tumor regression in both subcutaneous and intracranial lesions with no abnormal signs such as skin keratosis shown in osimertinib-treated mice. Plasma half life of YH25448 was 5.9-6.8 hr and tumor to plasma AUC0-last ratio was 3.0-5.1 in tumor bearing mice. YH25448 also showed excellent penetration of the BBB, achieving CSF concentrations exceeding the IC50 value for pEGFR inhibition in the tumor-bearing mice. Taken together, these findings suggest important role for the further development of YH25448 as a novel therapeutic for the treatment of EGFR mutant-positive NSCLC patients with brain metastases. Citation Format: Jiyeon Yun, Min Hee Hong, Seok-Young Kim, Chae Won Park, So-Young Kim, Mi Ran Yun, Han Na Kang, Kyoung-Ho Pyo, Jong Sung Koh, Ho-Juhn Song, Young- Sung Lee, Se-Woong Oh, Soongyu Choi, Byoung-Chul Cho. YH25448, an irreversible 3rd generation EGFR TKI, exhibits superior anticancer effects with potent brain BBB penetration in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4790.
    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: 2018
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1216-1216
    Abstract: The number of lung cancer patients is increasing every year worldwide. For these patients' treatment, not only anticancer drugs but also immune anticancer drugs are rapidly being developed. So far, the PD-1 antibody is widely used in treating NSCLC patients, and various pharmaceutical companies are continuously developing it. However, in PD-L1 low or negative patients, new drugs are required because there are no appropriate drugs. Of course, the PD-1 antibody is sometimes used, but the response rate is low, so new therapeutic drugs are needed.We identified a new target for PD-L1 low or negative patients using PD-L1 negative or positive lung cancer tissues. The new target's code name is "Target protein A." Target protein A expressed higher in tumor than normal. As a result of analyzing caucasian lung cancer patients' tissues by immunohistochemistry, 36% of cases expressed "Target protein A". Moreover, we also confirmed that target protein A was higher in tumors than normal through the TCGA database. Based on these results, we developed an immune anticancer drug (WM-A1) targeting Target protein A and demonstrated that it induces cancer cell death by inhibiting the binding with the binding partner protein B. Meanwhile, to clarify the relationship between PD-L1 and Target protein A, we analyzed the expression between the two proteins in lung cancer cell lines and proved that they exhibit reverse correlation. Among PD-L1 low or negative lung cancer patient tissues, about 32.75% of tissues expressed Target protein A. Conversely, among the patient samples expressing Target protein A, the PD-L1 low or negative population was 63%. We checked a similar trend through the TCGA database. For the efficacy of WM-A1, we confirmed that WM-A1 induced T cell-mediated cell death in a co-culture system with human PBMC and secreted major cytokines. In addition, we revealed that the group transplanted with a cell line expressing Target protein A in the PBMC humanized model showed high immuno-anticancer efficacy. Furthermore, we demonstrated that WM-A1 increased T cell activation and related cytokine expression. However, there was no reactivity to the PD-1 antibody because it expressed Target protein A and did not express PD-L1.Therefore, we suggest that WM-A1 is a new therapeutic antibody for the PD-L1 low or negative patient population. Based on these findings, we are planning a preclinical study (GLP-Tox) in 2021. #Corresponding author: Dong-Hoon Jin*These authors (Hye jin Son and Minki Lee) contributed equally to this work. Citation Format: Hye jin Son, Minki Lee, Seongrak Kim, Jai-Hee Moon, Hana Kim, Wonhwa Shin, Joseph Kim, Mi So Lee, Daeun Kim, Seunggeon Bae, Joonyee Jeong, Seung-Woo Hong, Chun-Ho Park, Hyun Ho Lee, Dong-Hoon Jin. New therapeutic antibody ("WM-A1") for treatment of low or no PD-L1 NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1216.
    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: 2021
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