Translational Cancer Biology Laboratory

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The Translational Cancer Biology (TCB) Laboratory is focused on developing biological correlates relevant to clinical trials and the translational arena, and on establishing an interface between engineering and medicine. Specific areas include:

1. Circulating cancer markers; e.g. circulating tumour cells (CTC). The laboratory has been developing CTC technologies in collaboration with the NUS Mechanobiology Institute and local start-up companies, such as Clearbridge Biomedics. We are looking at the utility of these markers in the establishment of diagnosis and during treatment, and their potential utility as screening tools in conjunction with existing screening technologies, such as low-dose computed tomography in lung cancer.
   
   
2. Establishing in vitro primary cell line cultures. The laboratory has established ovarian disease models across a variety of malignant and benign ovarian conditions. These models will be used to understand the biological progression of disease and for discovery of novel drug targets relevant to the disease model. We are expanding this into other tumour histologies and collaborating with like-minded investigators on humanised mouse models.
   
   
3. Extracellular matrix signatures relevant to cancer. We adopted a big data approach to differential gene expression and mining public data, and have described a novel gene expression signature that prognosticates across lung and other cancer types. We are now looking into correlating this signature in CTCs for metastasis, and examining gene expression changes in whole tumours to draw relations to the immune response and the development of resistance.

Dr. Darren Lim is a clinician-scientist awardee and senior Principal Investigator at IMCB, A*Star. He is an active international clinical trialist, and is Clinical and Scientific Director, Investigational Medicine Unit, SingHealth. The laboratory is supported by an NMRC Clinician Scientist Award, Industrial Alignment Funds, and IMCB core funding.

Selected publications:

1. Yeo T, Tan SJ, Lim CL, et al. Microfluidic enrichment for the single-cell analysis of circulating tumor cells. Sci Rep. 2016;6:22076.
2. Tan CL, Lim TH, Lim TK, et al. Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer. Oncotarget. 2016;7:23251–23262.
3. Soh SX, Siddiqui FJ, Allen JC, et al. A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer. Oncotarget. 2017;8:41474–41486.
4. Lim SB, Tan SJ, Lim WT, Lim CT. An extracellular matrix-related prognostic and predictive indicator for earlystage non-small cell lung cancer. Nat Commun. 2017;8:1734.
5. Lim SB, Tan SJ, Lim WT, Lim CT. A merged lung cancer transcriptome dataset for clinical predictive modeling. Sci Data. 2018;5:180136.
6. Ma BB, Lim WT, Goh BC, et al. Antitumor activity of nivolumab and biomarkers in recurrent and metastatic nasopharyngeal carcinoma: An international multicenter study of the Mayo Clinic Phase 2 Consortium (NCI-9742, NCT02339558). J Clin Oncol. 2018;36:1412–1418.
7. Bin Lim S, Chua MLK, Yeong JPS, Tan SJ, Lim WT, Lim CT. Pan-cancer analysis connects tumor matrisome to immune response. NPJ Precis Oncol. 2019;3:15.
8. Lim SB, Tan SJ, Lim WT, Lim CT. Compendiums of cancer transcriptomes for machine learning applications. Sci Data. 2019;6(1):194
9. Lim SB, Lee WD, Vasudevan J, Lim WT, Lim CT. Liquid biopsy: one cell at a time. NPJ Precis Oncol. 2019;3:23. 3. Wang Z, Yip LY, Lee JHJ, et al. Methionine is a metabolic dependency of tumor-initiating cells. Nat Med. 2019;25(5):825-837.
10. Lim SB, Lim CT, Lim WT. Single-Cell Analysis of Circulating Tumor Cells: Why Heterogeneity Matters. Cancers (Basel). 2019;11(10):1595.
11. Lim SB, Yeo T, Lee WD, Bhagat AAS, Tan SJ, Tan DSW, Lim WT, Lim CT. Addressing cellular heterogeneity in tumor and circulation for refined prognostication. Proc Natl Acad Sci U S A. 2019;116(36):17957-17962.
12. M Schuler, R Berardi, WT Lim, M de Jonge, TM Bauer, A Azaro, M Gottfried, JY Han, DH Lee, M Wollner, DS Hong, A Vogel, A Delmonte, M Akimov, S Ghebremariam, X Cui, N Nwana, M Giovannini, TM Kim. Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial Ann Oncol 31(6), 789-797. 2020 https://doi.org/10.1016/j.annonc.2020.03.293
13. WN Liu, SY Fong, WWS Tan, SY Tan, M Liu, JY Cheng, S Lim, L Suteja, EK Huang, JKY Chan, NG Iyer, JPS Yeong, DWT Lim, QF Chen. Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy. Cancers 12(4) 1025. 2020. doi.org/10.3390/CANCERS12041025
14. Kong SL, Liu X, Tan SJ, Tai JA, Phua LY, Poh HM, Yeo T, Chua YW, Haw YX, Ling WH, Ng RCH, Tan TJ, Loh KWJ, Tan DS, Ng QS, Ang MK, Toh CK, Lee YF, Lim CT, Lim TKH, Hillmer AM, Yap YS, Lim WT. Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer. Front Oncol. 2021 Jul 16;11:698551. doi: 10.3389/fonc.2021.698551.
15. MK Ang, JE Montoya, E, Tharavichitkul, …WT Lim. A phase II study of nimotuzumab (TheraCim-hR3) concurrent with cisplatin/radiotherapy in patients with locally advanced head and neck squamous cell carcinoma. Head and Neck-DOI: 10.1002/HED.26635GC
16. DWT Lim, CK Toh, S Chia, SYN Tang, Y Cheng, KH Seow, L Zhou. MicroRNA-Profiling Based Screening of Non-small-cell Lung Cancer in Plasma. IRC-SET, 295-306, 2020
17. Mai, Hai-Qiang; Chen, Qiu-Yan; Chen, Dongping;… Lim, Wan-Teck,...et al. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nature Medicine, 2021. DOI: 10.1038/S41591-021-01444-0
18. Lim, Darren Wan-Teck; Ng, Dorothy Hui Lin; Low, Jenny Guek-Hong. Bacillus Calmette-Guerin scar flare after an mRNA SARS-CoV-2 vaccine. Canadian Medical Association Journal, 2021. DOI: 10.1503/CMAJ.210696
19. Piha-Paul SA, Geva R, Tan TJ, Lim DW, Hierro C, Doi T, Rahma O, Lesokhin A, Luke JJ, Otero J, Nardi L, Singh A, Xyrafas A, Chen X, Mataraza J, Bedard PL. First-in-human phase I/Ib open-label dose-escalation study of GWN323 (anti-GITR) as a single agent and in combination with spartalizumab (anti-PD-1) in patients with advanced solid tumors and lymphomas. J Immunother Cancer. 2021 Aug;9(8):e002863. doi: 10.1136/jitc-2021-002863.
20. Teng YHF, Quah HS, Suteja L, Dias JML, Mupo A, Bashford-Rogers RJM, Vassiliou GS, Chua MLK, Tan DSW, Lim DWT, Iyer NG. Analysis of T cell receptor clonotypes in tumor microenvironment identifies shared cancer-type-specific signatures. Cancer Immunol Immunother. 2021 Sep 27:1–10. doi: 10.1007/s00262-021-03047-7. Epub ahead of print. Erratum in: Cancer Immunol Immunother. 2021 Oct 22;: PMID: 34580764
21. Belotti Y, Lim SB, Iyer NG, Lim WT, Lim CT. Prognostic Matrisomal Gene Panel and Its Association with Immune Cell Infiltration in Head and Neck Carcinomas. Cancers (Basel). 2021 Nov 17;13(22):5761. doi: 10.3390/cancers13225761. PMID: 34830910
22. Even C, Wang HM, Li SH, Ngan RK, Dechaphunkul A, Zhang L, Yen CJ, Chan PC, Chakrabandhu S, Ma BBY, Tanasanvimon S, Lee VHF, Lou PJ, Li Z, Spira AI, Sukari A, Guigay J, McCune S, Gonzalez-Maffe J, Szpakowski S, Yao Y, Liang H, Mataraza J, Séchaud R, Manenti L, Lim DW. Phase II, Randomized Study of Spartalizumab (PDR001), an Anti-PD-1 Antibody, versus Chemotherapy in Patients with Recurrent/Metastatic Nasopharyngeal Cancer. Clin Cancer Res. 2021 Dec 1;27(23):6413-6423. doi: 10.1158/1078-0432.CCR-21-0822. Epub 2021 Aug 25. PMID: 34433653.
23. Goh KY, Lau KW, Cheng TY, Tham SC, Lim CT, Iyer NG, Lim SB, Lim DW. Matrisomal genes in squamous cell carcinoma of head and neck influence tumor cell motility and response to cetuximab treatment. Cancer Commun (Lond). 2022 Apr;42(4):355-359. doi: 10.1002/cac2.12279. Epub 2022 Mar 2. PMID: 35234368