Laboratory Introduction - Overview - Seoul National University Cancer Research Institute

Laboratory of Translational Oncology for Precision Medicine

We are actively conducting translational research for the advance of cancer precision medicine by applying cancer genomics and molecular biology techniques. In ‘bedside to bench’ approach, we incorporate cancer patients' clinicopathological resources and genomic data to elucidate the mechanism of response/resistance to anti-cancer agents including targeted agents. In ‘bench to bedside’ approach, we turn scientific insights into principles and concepts for clinical trials to maximize benefits for cancer patients in both survival and quality-of-life.

Our laboratory stems from ‘Laboratory of Experimental Therapeutics and Cancer Epigenetics’ led by emeritus professor Yung-Jue Bang, M.D., Ph.D. and has been evolving over the past 20 years. Through active collaboration among medical oncologists, clinical trial staffs, basic researchers and graduate students, we are setting the basis of precision oncology and tailored targeted therapy. As a world-class research laboratory, we also work closely with global pharmaceutical companies to investigate new molecular targeted agents and immune-modulating agents and to provide a scientific rationale for the early clinical trials in human cancer. Not only using blood and tumor tissue from real-world patients, we are establishing various cancer models including cell lines, organoids, animal models, and patient-derived xenografts. We apply various cytotoxic, targeted, and immunologic drugs to the cancer models to set up basis for maximal synergy between ‘bench’ and ‘bedside’ part.

Related Researcher

Seock-Ah Im Professor

Email : moisa@snu.ac.kr
Papers Laboratory

Kyung-Hun Lee Professor

Email : kyunghunlee@snu.ac.kr
Papers Laboratory

Research topics

· Antitumor activity, action mechanism, and predictive biomarker for targeted therapies related to oncogenic pathways in breast cancer, gastric cancer, and gastrointestinal stromal tumors

· Antitumor activity with response mechanism research for DNA damage response (DDR)-targeted agents and antibody-drug conjugates (ADCs) in solid tumors including breast cancer and gastric cancer

· Efficacy of cell cycle inhibitors or modulators in breast cancer and gastric cancer models

· Resistance mechanism to targeted therapies and strategies to overcome

· Translational research using clinical resources such as tumor samples and blood

· Genomics and multi-omics integrated approaches for breast cancer

Research goals

To develop molecularly-tailored precision medicine strategies and provide new insights in biology of solid tumors.
1. To understand the mechanisms in response/resistance to drugs targeting oncogenic pathways including DNA damage repair and cell cycle checkpoints utilizing clinical and translational resources.
2. To apply scientific knowledge into proof-of-concept clinical trial not only to advance science but also to benefit patients.

Research achievements

· Homologous repair deficiency score for identifying breast cancers with defective DNA damage response. Min A, Kim K, Jeong K, Choi S, Kim S, Suh KJ, Lee KH, Kim S, Im SA. Sci Rep. 2020 Jul 27;10(1):12506.

· Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer. Ha DH, Min A, Kim S, Jang H, Kim SH, Kim HJ, Ryu HS, Ku JL, Lee KH, Im SA. Sci Rep. 2020 Jun 18;10(1):9930.

· Olaparib monotherapy for Asian patients with a germline BRCA mutation and HER2-negative metastatic breast cancer: OlympiAD randomized trial subgroup analysis. Im SA, Xu B, Li W, Robson M, Ouyang Q, Yeh DC, Iwata H, Park YH, Sohn JH, Tseng LM, Goessl C, Wu W, Masuda N. Sci Rep. 2020 May 29;10(1):8753.

· Prognostic Role of Androgen Receptor Expression in Surgically Resected Early Breast Cancer Patients. Yang Y, Min A, Lee KH, Ryu HS, Kim TY, Woo GU, Suh KJ, Lee DW, Lee HB, Moon HG, Han W, Park IA, Noh DY, Im SA. J Breast Cancer. 2020 Apr 20;23(2):182-193.

· PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation. Min A, Im SA. Cancers (Basel). 2020 Feb 8;12(2):394

· Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial. Park YH, Kim TY, Kim GM, Kang SY, Park IH, Kim JH, Lee KE, Ahn HK, Lee MH, Kim HJ, Kim HJ, Lee JI, Koh SJ, Kim JY, Lee KH, Sohn J, Kim SB, Ahn JS, Im YH, Jung KH, Im SA; Korean Cancer Study Group (KCSG). Lancet Oncol. 2019 Dec;20(12):1750-1759.

· Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva-Vazquez R, Jung KH, Chakravartty A, Hughes G, Gounaris I, Rodriguez-Lorenc K, Taran T, Hurvitz S, Tripathy D. N Engl J Med. 2019 Jul 25;381(4):307-316.

· Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. Im SA, Mukai H, Park IH, Masuda N, Shimizu C, Kim SB, Im YH, Ohtani S, Huang Bartlett C, Lu DR, Iyer S, Mori Y, Mori A, Gauthier E, Finn RS, Toi M. J Glob Oncol. 2019 May;5:1-19.

· Prognostic effects of abnormal DNA damage response protein expression in breast cancer. Suh KJ, Ryu HS, Lee KH, Kim H, Min A, Kim TY, Yang Y, Lee HB, Moon HG, Han SW, Oh DY, Han W, Park IA, Noh DY, Im SA. Breast Cancer Res Treat. 2019 May;175(1):117-127.

· Androgen Receptor Inhibitor Enhances the Antitumor Effect of PARP Inhibitor in Breast Cancer Cells by Modulating DNA Damage Response. Min A, Jang H, Kim S, Lee KH, Kim DK, Suh KJ, Yang Y, Elvin P, O'Connor MJ, Im SA. Mol Cancer Ther. 2018 Dec;17(12):2507-2518.

· Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells. Lee M, Lee KH, Min A, Kim J, Kim S, Jang H, Lim JM, Kim SH, Ha DH, Jeong WJ, Suh KJ, Yang YW, Kim TY, Oh DY, Bang YJ, Im SA. Cancer Res Treat. 2019 Apr;51(2):451-463.

· Cyclin E overexpression confers resistance to the CDK4/6 specific inhibitor palbociclib in gastric cancer cells. Min A, Kim JE, Kim YJ, Lim JM, Kim S, Kim JW, Lee KH, Kim TY, Oh DY, Bang YJ, Im SA. Cancer Lett. 2018 Aug 28;430:123-132.

· AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells. Min A, Im SA, Jang H, Kim S, Lee M, Kim DK, Yang Y, Kim HJ, Lee KH, Kim JW, Kim TY, Oh DY, Brown J, Lau A, O'Connor MJ, Bang YJ. Mol Cancer Ther. 2017 Apr;16(4):566-577.

· Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells. Kim HJ, Min A, Im SA, Jang H, Lee KH, Lau A, Lee M, Kim S, Yang Y, Kim J, Kim TY, Oh DY, Brown J, O'Connor MJ, Bang YJ. Int J Cancer. 2017 Jan 1;140(1):109-119.

· Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis. Kim S, Min A, Lee KH, Yang Y, Kim TY, Lim JM, Park SJ, Nam HJ, Kim JE, Song SH, Han SW, Oh DY, Kim JH, Kim TY, Hangauer D, Lau JY, Im K, Lee DS, Bang YJ, Im SA. Cancer Res Treat. 2017 Jul;49(3):643-655.

· Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances anti-tumor effects of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in triple-negative breast cancer cells. Min A, Im SA, Kim DK, Song SH, Kim HJ, Lee KH, Kim TY, Han SW, Oh DY, Kim TY, O'Connor MJ, Bang YJ. Breast Cancer Res. 2015 Mar 7;17:33.

· RAD51C-deficient cancer cells are highly sensitive to the PARP inhibitor olaparib. Min A, Im SA, Yoon YK, Song SH, Nam HJ, Hur HS, Kim HP, Lee KH, Han SW, Oh DY, Kim TY, O'Connor MJ, Kim WH, Bang YJ. Mol Cancer Ther. 2013 Jun;12(6):865-77.

· Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer. Nam HJ, Im SA, Oh DY, Elvin P, Kim HP, Yoon YK, Min A, Song SH, Han SW, Kim TY, Bang YJ. Mol Cancer Ther. 2013 Jan;12(1):16-26.

· Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Domchek SM, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, Alexandre J, You B, Bastian S, Krebs MG, Wang D, Waqar SN, Lanasa M, Rhee J, Gao H, Rocher-Ros V, Jones EV, Gulati S, Coenen-Stass A, Kozarewa I, Lai Z, Angell HK, Opincar L, Herbolsheimer P, Kaufman B. Lancet Oncol. 2020 Sep;21(9):1155-1164.

· Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Emens LA, Esteva FJ, Beresford M, Saura C, De Laurentiis M, Kim SB, Im SA, Wang Y, Salgado R, Mani A, Shah J, Lambertini C, Liu H, de Haas SL, Patre M, Loi S. Lancet Oncol. 2020 Oct;21(10):1283-1295.

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