Overview
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Overview
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Laboratory Introduction
Laboratory Introduction
Translational Research Laboratory
Translational Research Laboratory
Translational Research Laboratory is cunducting various basic and medical cancer research by applying molecular-biological methods. Until the 1900s, the research in cancer was the study of cytotoxic anti-cancer agents using cancer cell lines. With the advent of targeted therapeutics since the 2000s, the paradigm of cancer research has changed to evaluation of efficacy and cytotoxicity of targeted therapies, development of clinical biomarkers, and strategies to overcome drug resistance. In our lab, we have established immortal cancer cell lines of gastric cancer, biliary tract cancer, and pancreatic cancer obtained from cancer patients clinically. Since these cell lines have various molecular/genetic characteristics of actual cancer patients, they can be usefully used in the development of new targeted therapies. Our lab is actively providing the rationale for the development of novel targeted therapeutics with these self-established cancer cell lines. Recently, various therapeutic agents targeting HER2, DNA damage repair pathway and cancer-immune system have been researched and developed. Our lab is actively conducting research to identify antitumor effects, action mechanisms and biomarkers of these newly developed therapeutics in cooperation with numbers of pharmaceutical companies. And we present the preclinical rationale for clinical trial design. In addition to these basic studies, the important thing is to be improved to help the clinical field. For applying the results of basic research to clinical field directly, it is essential to bench-to-clinic and translational research using human-derived materials. Our lab designs and conducts clinical trials based on the biomarkers and secures human-derived materials. Therefore, we clinically verified the pre-clinical results of bench study in patients through the analysis of human-derived materials. Moreover, we developed another clinical trial and provided the basis for applying the results to the linical field. In sum, Translational Research Laboratory is researching the mechanism of action and resistance of various targeted therapeutic agents through cooperation with leading pharmaceutical companies using several cell lines and self-established cancer cell lines and is actively developing biomarkers related to effects and cytotoxicity. have. In addition, we are performing several clinical trials based on various targeted therapeutics and cancer immunotherapeutic agents, and through the collection and analysis of human materials, we verify the results revealed in preclinical studies in actual patients and contribute to the development of new drugs.
Related Researcher
Do-Youn Oh Professor
- Email : ohdoyoun@snu.ac.kr
Research topics
1. Efficacy and biomarker validation studies of targeted therapeutics related to various oncogenic pathways in gastric cancer, biliary tract cancer, and pancreatic cancer. 2. Observational study on the effect of DNA damage response target substances on immunomodulatory action in gastric cancer, biliary tract cancer, and pancreatic cancer and its antitumor effect. 3. Research on resistance mechanism according to targeted therapeutics and study for overcoming strategies. 4. Research to identify biomarkers in blood required for targeted therapeutics using clinical resources such as patient-derived cancer tissues and blood samples.
Research goals
The goal of this laboratory is to reveal the biological characteristics of each cancer type and to contribute to enhancing the therapeutic effect of targeted therapeutics by identifying the role of the oncogenic pathway specific to gastric cancer, biliary tract cancer, and pancreatic cancer. Ultimately, we will try to increase the success rate of clinical research and improve the patient's prognosis by presenting a personalized treatment design for each patient based on biomarkers.
Research achievements
- Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. Oh DY, Algazi A, Capdevila J, Longo F, Miller W Jr, Chun Bing JT, Bonilla CE, Chung HC, Guren TK, Lin CC, Motola-Kuba D, Shah M, Hadoux J, Yao L, Jin F, Norwood K, Lebellec L. Cancer. 2023 Apr 15;129(8):1195-1204.
- Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. Tempero MA, Pelzer U, O'Reilly EM, Winter J, Oh DY, Li CP, Tortora G, Chang HM, Lopez CD, Bekaii-Saab T, Ko AH, Santoro A, Park JO, Noel MS, Frassineti GL, Shan YS, Dean A, Riess H, Van Cutsem E, Berlin J, Philip P, Moore M, Goldstein D, Tabernero J, Li M, Ferrara S, Le Bruchec Y, Zhang G, Lu B, Biankin AV, Reni M; APACT Investigators. J Clin Oncol. 2023 Apr 10;41(11):2007-2019
- Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. J Clin Oncol. 2022 Dec 1;40(34):3929-3939.
- Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Meric-Bernstam F, Beeram M, Hamilton E, Oh DY, Hanna DL, Kang YK, Elimova E, Chaves J, Goodwin R, Lee J, Nabell L, Rha SY, Mayordomo J, El-Khoueiry A, Pant S, Raghav K, Kim JW, Patnaik A, Gray T, Davies R, Ozog MA, Woolery J, Lee KW. Lancet Oncol. 2022 Dec;23(12):1558-1570.
- Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Maio M, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, Cassier PA, Bariani GM, De Jesus Acosta A, Doi T, Longo F, Miller WH, Oh DY, Gottfried M, Xu L, Jin F, Norwood K, Marabelle A. Ann Oncol. 2022 Sep;33(9):929-938.
- A synthetic lethal strategy using PARP and ATM inhibition for overcoming trastuzumab resistance in HER2-positive cancers. Oh KS, Nam AR, Bang JH, Seo HR, Kim JM, Yoon J, Kim TY, Oh DY. Oncogene.2022 Aug;41(32):3939-3952.
- Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Maio M, Amonkar MM, Norquist JM, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, Cassier PA, Bariani GM, De Jesus Acosta A, Doi T, Longo F, Miller WH Jr, Oh DY, Gottfried M, Wang R, Norwood K, Marabelle A. Eur J Cancer. 2022 Jul;169:188-197.
- Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. Do-Youn Oh, Aiwu Ruth He, Shukui Qin, Li-Tzong Chen, Takuji Okusaka, Arndt Vogel, Jin Won Kim, Thatthan Suksombooncharoen, Myung Ah Lee, Masayuki Kitano, Howard Burris, Mohamed Bouattour, Suebpong Tanasanvimon, Mairéad G. McNamara, Renata Zaucha, Antonio Avallone, Benjamin Tan, Juan Cundom, Choong-kun Lee, Hidenori Takahashi, Masafumi Ikeda, Jen-Shi Chen, Julie Wang, Mallory Makowsky, Nana Rokutanda, Philip He, John F. Kurland, Gordon Cohen and Juan W. Valle for the TOPAZ-1 Investigators. NEJM Evid. 2022; 1 (8)
- Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer. Seo HR, Nam AR, Bang JH, Oh KS, Kim JM, Yoon J, Kim TY, Oh DY. Cancer Res Treat. 2022 Apr;54(2):541-553.
- Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Lancet Oncol. 2022 Feb;23(2):234-247.
- ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer. Nam AR, Yoon J, Jin MH, Bang JH, Oh KS, Seo HR, Kim JM, Kim TY, Oh DY. Cancer Res Treat. 2021 Oct;53(4):1096-1103.
- WEE1 inhibition reverses trastuzumab resistance in HER2-positive cancers. Jin MH, Nam AR, Bang JH, Oh KS, Seo HR, Kim JM, Yoon J, Kim TY, Oh DY. Gastric Cancer. 2021 Sep;24(5):1003-1020.
- Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study. Tempero M, Oh DY, Tabernero J, Reni M, Van Cutsem E, Hendifar A, Waldschmidt DT, Starling N, Bachet JB, Chang HM, Maurel J, Garcia-Carbonero R, Lonardi S, Coussens LM, Fong L, Tsao LC, Cole G Jr, James D, Macarulla T. Ann Oncol. 2021 May;32(5):600-608.
- Targeting Hypoxia Using Evofosfamide and Companion Hypoxia Imaging of FMISO-PET in Advanced Biliary Tract Cancer. Yoon J, Kang SY, Lee KH, Cheon GJ, Oh DY. Cancer Res Treat. 2021 Apr;53(2):471-479.
- The prognostic role of soluble transforming growth factor-β and its correlation with soluble programmed death-ligand 1 in biliary tract cancer. Kim JW, Lee KH, Kim JW, Suh KJ, Nam AR, Bang JH, Jin MH, Oh KS, Kim JM, Kim TY, Oh DY. Liver Int. 2021 Feb;41(2):388-395.
- Prospective evaluation of metabolic intratumoral heterogeneity in patients with advanced gastric cancer receiving palliative chemotherapy. Yoo SH, Kang SY, Yoon J, Kim TY, Cheon GJ, Oh DY. Sci Rep. 2021 Jan 12;11(1):296.
- Biliary tract cancer. Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Lancet. 2021 Jan 30;397(10272):428-444.
- The prognostic role of soluble TGF-beta and its dynamics in unresectable pancreatic cancer treated with chemotherapy. Park H, Bang JH, Nam AR, Park JE, Jin MH, Bang YJ, Oh DY. Cancer Med. 2020 ;9(1):43-51. N Engl J Med.2020 Jun 18;382(25):2419-2430.
- Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. N Engl J Med. 2020 June;382:2419-2430
- HER2-targeted therapies - a role beyond breast cancer. Oh DY, Bang YJ. Nat Rev Clin Oncol. 2020 Jan;17(1):33-48
- Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer. Cancer Res Treat. Jin MH, Nam AR, Park JE, Bang JH, Bang YJ, Oh DY. Cancer Res Treat. 2020 Jan;52(1):149-166.
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