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  • American Association for Cancer Research (AACR)  (51)
  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 119-119
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 119-119
    Abstract: Purpose: To investigate whether the overexpression of SOCS-1 affects radiosensitivity, invasion, and metastasis in xenograft nude mouse model. Methods: We established stable SOCS-1-overexpressing ME-180 cell line with pLNCX2-mSOCS1-Myc. Also we established xenograft nude mouse model for tumor growth delay experiment. Immunohistochemistry was employed to elucidate the pattern of expression of VEGF, CD-31, MMP-2, and TUNEL assay for apoptosis in SOCS-1 overexpressing ME-180 cells. Tumor cells were injected to right thigh of mouse to form cancer mass. Lung metastasis assay was performed in day 45 and 60. Metastatic nodules in both lungs were obtained and counted for statistical analysis. Results: Tumor growth delay after 5 Gy radiation was observed in SOCS overexpressing tumor compared to wild type tumor but the difference did not show the statistical significance (p & gt;0.05, Mann-Whitney U test). Immunohistochemistry showed that decreased MMP-2 expression, decreased VEGF expression, decreased CD-31 expression, and significantly elevated index of apoptotic body in SOCS-1 overexpressing tumor. Lung metastasis assay showed statistically significant decrement of metastatic nodule count in SOCS-1 overexpressing tumor (p & lt;0.05, Mann-Whitney U test). Conclusion: Decrement of radiosensitivity was statistically insignificant in SOCS-1 overexpressing tumor while invasion, angiogenesis, and metastasis were inhibited. Also apoptosis was increased in SOCS-1 overexpressing tumor. Citation Format: Moon-Hong Kim, Wonwoo Kim, Miae Kang, Hyesil Seol, Jae-Hoon Jeong. Overexpression SOCS-1 may inhibit invasion and metastasis of cervical cancer. [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 119. doi:10.1158/1538-7445.AM2014-119
    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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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 7 ( 2019-04-01), p. 1520-1534
    Abstract: Various miRNAs play critical roles in the development and progression of solid tumors. In this study, we describe the role of miR-204-5p in limiting growth and progression of breast cancer. In breast cancer tissues, miR-204-5p was significantly downregulated compared with normal breast tissues, and its expression levels were associated with increased survival outcome in patients with breast cancer. Overexpression of miR-204-5p inhibited viability, proliferation, and migration capacity in human and murine breast cancer cells. In addition, miR-204-5p overexpression resulted in a significant alteration in metabolic properties of cancer cells and suppression of tumor growth and metastasis in mouse breast cancer models. The association between miR-204-5p expression and clinical outcomes of patients with breast cancer showed a nonlinear pattern that was reproduced in experimental assays of cancer cell behavior and metastatic capacities. Transcriptome and proteomic analysis revealed that various cancer-related pathways including PI3K/Akt and tumor–immune interactions were significantly associated with miR-204-5p expression. PIK3CB, a major regulator of PI3K/Akt pathway, was a direct target for miR-204-5p, and the association between PIK3CB-related PI3K/Akt signaling and miR-204-5p was most evident in the basal subtype. The sensitivity of breast cancer cells to various anticancer drugs including PIK3CB inhibitors was significantly affected by miR-204-5p expression. In addition, miR-204-5p regulated expression of key cytokines in tumor cells and reprogrammed the immune microenvironment by shifting myeloid and lymphocyte populations. These data demonstrate both cell-autonomous and non-cell–autonomous impacts of tumor suppressor miR-204-5p in breast cancer progression and metastasis. Significance: This study demonstrates that regulation of PI3K/Akt signaling by miR-204-5p suppresses tumor metastasis and immune cell reprogramming in breast cancer.
    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: 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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  • 4
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 12, No. 11_Supplement ( 2013-11-01), p. A63-A63
    Abstract: Dysregulation of the PI3K-AKT & mTOR pathway by (mutation and/or) deletion of tumor suppressor gene PTEN frequently occurs in human prostate cancer and is therefore considered to be attractive molecule as therapeutic targets. Here, we investigated the antitumor effect of NVP-BEZ235 in human prostate cancer cells dependent on PTEN genotype. In this setting, NVP-BEZ235 induced cell death in the PTEN-independent manner. However, NVP-BEZ235 selectively induced apoptotic cell death in prostate cancer cells presenting wild-type PTEN, DU145, but not in cells with deletion of PTEN, PC3. Treatment with NVP-BEZ235 resulted in autophagic cell death in PC3 cells with PTEN loss of function. Consistently, NVP-BEZ235 treatment did not result in the cleavage of caspase-3 and was link to active LC3-I/II as an indicator of autophagic cell death process, suggesting an alternate route for induction of cell death after exposure to NVP-BEZ235 in PTEN-null prostate cancer cells. These results suggest that PTEN/PI3K/Akt pathways are critical for prostate cancer survival and targeting PI3K signaling by NVP-BEZ235 may be beneficial in prostate cancer independent on PTEN genotype. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A63. Citation Format: Jeong Eun Kim, Seoung-Woo Hong, Jae-Sik Shin, Jai-Hee Moon, Ye-Seul Kim, Kyu-pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Dong-Hoon Jin, Tae Won Kim. NVP-BEZ235, a dual PI3K/mTOR inhibitor, elicits an alternate route for induction of cell death in PTEN null prostate cancer cells. [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 A63.
    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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  • 5
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 14, No. 11 ( 2015-11-01), p. 2613-2622
    Abstract: The MET receptor tyrosine kinase, the receptor for hepatocyte growth factor (HGF), has been implicated in cancer growth, invasion, migration, angiogenesis, and metastasis in a broad variety of human cancers, including human hepatocellular carcinoma (HCC). Recently, MET was suggested to be a potential target for the personalized treatment of HCC with an active HGF–MET signaling pathway. However, the mechanisms of resistance to MET inhibitors need to be elucidated to provide effective treatment. Here, we show that HCC cells exhibit different sensitivities to the MET inhibitor PHA665752, depending on the phosphorylation status of FGFR. Treatment of cells expressing both phospho-FGFR and phospho-MET with the inhibitor PHA665752 did not cause growth inhibition and cell death, whereas treatment with AZD4547, a pan-FGFR inhibitor, resulted in decreased colony formation and cleavage of caspase-3. Moreover, silencing of endogenous FGFR1 and FGFR2 by RNAi of HCC cells expressing phospho-FGFR, phospho-FGFR2, and phospho-MET overcame the resistance to PHA665752 treatment. Treatment of primary cancer cells from patients with HCC expressing both phospho-FGFR and phospho-MET with PHA665752 did not induce cell death, whereas AZD4547 treatment induced cell death through the cleavage of caspase-3. In addition, treatment of cells resistant to PHA665752 with AZD4547 abrogated the activation of downstream effectors of cell growth, proliferation, and survival. On the basis of these results, we conclude that the FGFR pathway is critical for HCC survival, and that targeting this pathway with AZD4547 may be beneficial for the treatment of patients with HCC-expressing phospho-FGFR and phospho-MET. Mol Cancer Ther; 14(11); 2613–22. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 6
    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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  • 7
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 12, No. 11_Supplement ( 2013-11-01), p. C276-C276
    Abstract: Janus kinase (JAK) is one of the main upstream activators of signal transducers and activators of transcription (STAT) that are constitutively activated in various malignancies and are associated with cell growth, survival, and carcinogenesis. Here, we investigated to role of JAKs in colorectal cancer in order to develop effective therapeutic targets for ruxolitinib, which is the first JAK1/2 inhibitor to be approved by FDA. After examining the basal expression levels of phospho-JAK1 and phospho-JAK2, we measured the effects of ruxolitinib on the phosphorylation of JAK1/2 using western blot analysis. Cell viability was determined using the trypan blue exclusion assay. The cell death mechanism was identified by the activation of caspase 3 using western blot and annexin V staining. The basal levels of phospho-JAK1 and phospho-JAK2 were cancer cell type dependent. Colorectal cancer cell lines that phosphorylate both JAK1 and JAK2 include DLD-1 and RKO. Ruxolitinib inactivates both JAK1 and JAK2 in DLD-1 cells but inactivates only JAK1 in RKO cells. Cell death was proportional to the inactivation of JAK1 but not JAK2. Ruxolitinib causes caspase-dependent cell death, which is prevented by treatment with z-VAD. The inhibition of JAK1 phosphorylation seemed sufficient to allow ruxolitinib-mediated apoptosis. JAK1 is a key molecule that is involved in colon cancer cell survival and the inhibition of JAK1 by ruxolitinib results in caspase-dependent apoptosis in colorectal cancer cells. The use of selective JAK1 inhibitors could be an attractive therapy against colorectal cancer, but further clinical investigations are needed to test this possibility. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C276. Citation Format: Ho Jung An, Eun Kyoung Choi, Jin-Sun Kim, Seung-Woo Hong, Jai-Hee Moon, Jae-Sik Shin, Seung-Hee Ha, Kyu-Pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Eun Kyung Choi, Jung Shin Lee, Dong-Hoon Jin, Tae Won Kim. Ruxolitinib induces apoptotic cell death through the suppression of pJAK1 in human colon cancer cells. [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 C276.
    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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    SSG: 12
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  • 8
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 12, No. 11_Supplement ( 2013-11-01), p. C277-C277
    Abstract: Janus kinase (JAK) is one of the main upstream activators of signal transducers and activators of transcription (STAT) that are constitutively activated in various malignancies and are associated with cell growth, survival, and carcinogenesis. Here, we investigated to role of JAKs in colorectal cancer in order to develop effective therapeutic targets for INCB018424, which is the first JAK1/2 inhibitor to be approved by FDA. After examining the basal expression levels of phospho-JAK1 and phospho-JAK2, we measured the effects of INCB018424 on the phosphorylation of JAK1/2 using western blot analysis. Cell viability was determined using the trypan blue exclusion assay. The cell death mechanism was identified by the activation of caspase 3 using western blot and annexin V staining. The basal levels of phospho-JAK1 and phospho-JAK2 were cancer cell type dependent. Colorectal cancer cell lines that phosphorylate both JAK1 and JAK2 include DLD-1 and RKO. INCB018424 inactivates both JAK1 and JAK2 in DLD-1 cells but inactivates only JAK1 in RKO cells. Cell death was proportional to the inactivation of JAK1 but not JAK2. INCB018424 causes caspase-dependent cell death, which is prevented by treatment with z-VAD. The inhibition of JAK1 phosphorylation seemed sufficient to allow INCB018424-mediated apoptosis. JAK1 is a key molecule that is involved in colon cancer cell survival and the inhibition of JAK1 by INCB01424 results in caspase-dependent apoptosis in colorectal cancer cells. The use of selective JAK1 inhibitors could be an attractive therapy against colorectal cancer, but further clinical investigations are needed to test this possibility. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C277. Citation Format: Eun Kyoung Choi, Seung Hee Ha, Ho Jung An, Jin-Sun Kim, Seung-Woo Hong, Jai-Hee Moon, Jae-Sik Shin, Kyu-Pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Eun Kyung Choi, Jung Shin Lee, Dong-Hoon Jin, Tae Won Kim. INCB018424 induces apoptotic cell death through the suppression of pJAK1 in human colon cancer cells. [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 C277.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 19_Supplement ( 2013-10-01), p. B30-B30
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 19_Supplement ( 2013-10-01), p. B30-B30
    Abstract: The downstream events and target genes of p53 in senescence responses are not fully understood. Here, we identify a novel regulator, A-core gene, in p53-mediated cellular senescence. Overexpression of A-core in p53-deficient mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas A-core gene knockdown by small interfering RNA (siRNA) leads to escape from p53-mediated senescence in p53-expressing MEFs. A-core overexpression also increased intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued A-core overexpression-induced senescence. Surprisingly, the elevated levels of ROS that accompanied A-core overexpression were paralleled by an increase in p21 expression. siRNA-mediated knockdown of p21 in A-core overexpressing MEFs abrogated the A-core-dependent increase in ROS levels, indicating that A-core acts through p21 induction and subsequent ROS elevation to trigger senescence. In addition, expression of the cell proliferation-related proteins cyclin E and B was decreased after A-core expression. Collectively, these results suggest that A-core is a downstream target of p53 that is sufficient to induce p21 expression and ROS production, and is necessary for p53-mediated senescence. Citation Format: Jae-Sik Shin, Seung-Woo Hong, Dae-Hee Lee, Jai-Hee Moon, Jeong Eun Kim, Yong Sang Hong, Kyu-pyo Kim, Jae-Lyun Lee, Eun Kyung Choi, Jung Shin Lee, Dong-Hoon Jin, Tae Won Kim. Identification of new regulator in p53-mediated cellular senescence. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B30.
    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: 2013
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  • 10
    In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 9, No. 10 ( 2019-10-01), p. 1388-1405
    Abstract: The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RICTOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), adavosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib. Significance: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility. This article is highlighted in the In This Issue feature, p. 1325
    Type of Medium: Online Resource
    ISSN: 2159-8274 , 2159-8290
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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