Tan Chin Tuan Lab of Optical Imaging and Photodynamic & Proton Therapy

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The focus of our laboratories, which is led by two clinician-scientists, centres on four topics in two dominant cancers in Singapore—prostate cancer (3rd most common) and nasopharynx (NPC) and head and neck cancers (7th most common among males). These topics are:

1) To characterise the molecular landscape of radioresistant and lethal metastatic prostate and head and neck cancers;

2) To develop novel prognostic and predictive biomarkers in these tumour types to improve clinical stratification and precise treatment matching;

3) To apply novel therapeutic strategies clinically, including proton beam therapy (PBT), photodynamic therapy (PDT), and targeted drugs/nanotherapeutics to improve the therapeutic ratio of these modalities in the management of treatment-refractory tumours; and, finally,

4) To incorporate large “–omics” datasets, including molecular (genomics, epigenomics, transcriptomics), pathological, and imaging (radiomics) datasets to build robust models that can personalise risk stratification and therapies in patients with these cancers.

Our research activities are largely funded by several national-level and institutional grants (NRF CRP, MOE Tier 3, NMRC CSA). Of note, we are the Lead PIs on a National-level project that is being funded by the National Research Foundation exploring the radiobiological effects of PBT.

Amongst our key discoveries in the different topics, our group has;

1) Developed a novel prognostic index (PRANCIS –http://PRANCIS.Medlever.com) from a Big data registry to personalise treatment recommendations for patients with radioresistant NPC;

2) Initiated a clinical programme for PDT in patients with recurrent head and neck cancers, who have failed all other lines of treatment; and

3) Completed several phase 2 and 3 clinical trials in advanced NPC that led to shifts in standards of care; among the pivotal trials were a) demonstrating the survival advantage with the use of induction chemotherapy in stage 3-4 NPC (NEJM 2019) and b) demonstrating the survival advantage with local radiotherapy in metastatic NPC patients (JAMA Oncol 2020).

Selected publications:

1. Guo Y-M, Chen J-R, Feng Y-C, Chua ML, et al. Germline polymorphisms and length of survival of nasopharyngeal carcinoma: An exome-wide association study in multiple cohorts. Adv Sci (Weinh) 2020; 7(10): 1903727

2. Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen Y-P, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li GJ, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Liu N, Li YQ, Chua ML, et al. Gemcitabine and cisplatin induction chemotherapy nasopharyngeal carcinoma. N Engl J Med 2019; 381(12): 1124-35.

3. Espiritu SM, Liu L, Rubanova Y, et al. The Evolutionary Landscape of Localized
Prostate Cancers Drives Clinical Aggression. Cell. 2018;173:1003–1013. e15.

4. Li YQ, Tian YM, Tan SH, , et al. A Prognostic Model for Stratification of Radioresistant Nasopharynx Cancer to Curative Salvage Radiotherapy. J Clin Oncol. 2018;36:891–899.

5. Fraser M, Sabelnykova V, Yamaguchi TN, et al. Genomic hallmarks of localized,
non-indolent prostate cancer. Nature. 2017;541:359–364.

6. Chua ML, Lo W, Pintilie M, et al. A Prostate Cancer “Nimbosus”: Genomic
instability and SChLAP1 dysregulation underpins aggression of intraductal and
cribriform sub-pathologies. Eur Urol. 2017; 72:665–674. (Accorded Platinum Priority and Cover Page of Issue)

7. Chua ML, Wee J, Hui EP, Chan AT. Nasopharyngeal carcinoma. Lancet. 2016;387:1012–1024.