Research 

Laboratory Focus

The focus of our laboratory centers on two dominant cancers in Singapore, namely prostate (3rd most common among males) and nasopharynx and head and neck cancers (7th most common among males). 

We aim to:

1. To characterize the molecular landscape of radioresistant and lethal metastatic prostate and head and neck cancers.

2. Develop novel prognostic and predictive biomarkers in these tumor types to improve clinical stratification and precise treatment matching.

3. Apply clinical application of novel therapeutic strategies, 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 tumors.

4. Incorporate large “–omics” datasets, including molecular (genomics, epigenomics, transcriptomics), pathology, and imaging (radiomics) to build robust models to personalize risk stratification and therapies in patients with these cancers.

Precision radiotherapy has significantly advanced cure rates of NPC and prostate cancers. However, 20-30% of cancers still recur locally despite radiotherapy treatment. Currently for these recurring cancer patients, therapeutic options are very limited, highlighting the need for improved clinical stratification to identify the patients whose cancers are likely to recur, and for novel therapeutics to improve cure rate. In our lab, we aim to analyze and compare the genomic profiles in pre- and post- radiotherapy treatment tumors in recurrent NPC and prostate cancer cases to define the mutations that drive the cancer development and provide cancer cells with radio-resistance, i.e. an ability to resist to radiotherapy treatment. Once identified, we will test if these mutations could serve as novel “druggable/treatable” targets for newly developed therapeutic agents.

Nasopharynx Cancer 

In the area of NPC genomics, we have developed strong partnership with the Sun Yat-Sen University Cancer Center (SYSUCC) in Guangzhou, China, to perform deep molecular profiling of 1,000 cases, so as to re-define the molecular taxonomy of NPC, and to determine the molecular phenotypes that are associated with tumor aggression. Separately, we have developed a novel prognostic index (PRANCIS – http://PRANCIS.Medlever.com) to stratify radioresistant NPC patients into two risk groups with disparate survival of 70% (low-risk) vs 20% (high-risk) at 3 years; this has since led to widespread clinical adoption at both institutions in selecting appropriate patients with recurrent NPC for a repeat course of radiotherapy. A prospective clinical trial is currently being planned.

Additionally, as part of a Big Data initiative in NPC, we are exploring the role of radiomics as a parallel domain to inform on tumour biology and clinical stratification. In this aspect, we collaborate with two European Centres – Gemeli ART, Milan (Prof Vincenzo Valentini) and OncoRay, Dresden (Prof Steffen Lock). Our efforts are focused on harmonization and development of two pipelines - PyRADIOMICS and MODDICOM for in-depth radiomics analyses of CT, MRI, PET, and real-time treatment-captured cone-beam CT images for adaptive radiotherapy planning in NPC patients (Gemeli ART), as well as development of an AI deep-learning platform for prognostic model development (OncoRay).

Prostate Cancer 

For prostate cancer, we have developed a strong partnership with Ontario Institute for Cancer Research and Sunnybrook Research Institute at Canada, and have been involved in the ICGC-sanctioned Canadian Prostate Cancer Gene Network (CPC-GENE), which aims to derive a comprehensive molecular landscape of localized prostate cancer, and test if these molecular hallmarks improve clinical stratification. Additionally, we have joined the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) research consortium, which consists 120 universities and research institutes across different continents. Here, we aim to investigate for 1) demographic differences in prostate cancer risk susceptibility, and 2) unique germline-somatic genomic linkage in Asian prostate cancers.

Another component of our programme involves investigating the immune response that is induced by radiotherapy. We also seek to interrogate if type of immunotherapy and sequencing of treatment result in differential activation of the immune response. Of note, for this part, we collaborate with a local biotechnology spin-off from A*Star – immunoSCAPE to exploit their expertise in mass cytometry time-of-flight (CyTOF) to map at a very deep level the immune repertoire following radiotherapy and immuno-radiotherapy (IO-RT).

Photodynamic Therapy 

Lastly, in the domain of novel cancer therapeutics, our lab is interested in utilizing photodynamic therapy (PDT) in the treatment of recurrent head and neck cancers. In order to achieve better therapeutic ratio with PDT, we are investigating the combination of targeted agents such as small molecule inhibitors of angiogenesis and immunotherapy. We also have a long-term collaboration with Prof Zhang Yong, NUS Bioengineering Faculty to develop nanoparticle-based novel delivery systems and photosensitizers. In this space, we have translated our preclinical studies into the clinic to the form of a prospective observational study in treatment-refractory head and neck cancer patients following intervention with PDT.