Cancers of the upper aerodigestive tracts are among the most frequent cancers, and understanding these diseases (of the head and neck and lung) have been the focus of Professor Goh’s research team over the past decade. Through a multi-disciplinary collaborative effort comprising of genomics, proteomics and high throughput technologies, his group aims to discover novel cancer biomarkers that could stratify high risk tumours for therapeutic intervention.

The current research in the group can be summarised into three main themes:

1) Plasma-based analysis for biomarker discovery.

Early cancer intervention is often challenging due to a lack of diagnostic biomarkers for early cancer detection. By applying quantitative proteomics and next generation sequencing on liquid biopsies collected from multicentre trial, the group aims to delineate diagnostic marker signatures for non-small cell lung cancer (NSCLC) and nasopharyngeal carcinomas (NPC). Current work on plasma exosomes has identified blood-based signature panel for early detection of NSCLC.

2) Functional genomics in the understanding of cancer biology.

Comprehensive next generation sequencing technologies have allowed the group to identify genetic polymorphisms and rare somatic mutations among the NSCLC and head and neck cancers (HNC). Gene variants that affect drug disposition, protein structure and receptor interaction may have significant effects to account for ethnic or geographic differences in drug action. The team has identified recurring mutations of the c-MET receptor and p53 protein that are gain-of-function and responsible for malignant growth. Molecular dissection of tumour biology of these variants will be pursued to yield therapeutic targets for clinical development and drug repurposing.

3) Target identification for precision oncology.

The team is interested to explore novel targets within the hallmarks of cancer to design novel therapeutics strategies. Some of the recent work include targeting cancer metabolism through development of inhibitors of oxidative phosphorylation (OXPHOS) and STAT3 signaling, cell cycle inhibition using CDK4/6 blockers, antiangiogenic therapy coupled with chemotherapy, dendritic cell-based immunotherapy, and re-differentiation in radio-refractory cancers. These studies aim to bridge the gap between laboratory and clinic through trenchant analysis of tumour resistance, immune tolerance and metabolic rewiring.

1. Kim G, Tan HL, Sundar R, Lieske B, Chee CE, Ho J, Shabbir A, Babak MV, Ang WH, Goh BC, Yong WP, Wang L, So JBY. PIPAC-OX: A Phase I study of Oxaliplatin-based Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Peritoneal Metastases. Clin Cancer Res. 2020 Nov 4:clincanres.2152.2020. doi: 10.1158/1078-0432.CCR-20-2152. Epub ahead of print. PMID: 33148667.

2. Yap T, Tan DSP, Terbuch A, Caldwell R, Guo C, Goh BC, et al. First-in-human trial of the oral ataxia telangiectasia and Rad3-Related Inhibitor BAY 1895344 in patients with advanced solid tumours. Cancer Discov. 2020 Sep 28:CD-20-0868. doi: 10.1158/2159-8290.CD-20-0868. Online ahead of print.PMID: 32988960.

3. Chong WQ, Lim CM, Sinha AK, Tan CS, Chan GHJ, Huang Y, Barr Kumarakulasinghe N, Sundar R, Jeyasekharan AD, Loh WS, Tay JK, Yadav K, Wang L, Wong AL, Kong LR, Soo RA, Lau JA, Soon YY, Goh RM, Ho FCH, Chong SM, Lee SC, Loh KS, Tai BC, Lim YC, Goh BC. Integration of antiangiogenic therapy with cisplatin and gemcitabine chemotherapy in patients with nasopharyngeal carcinoma [published online ahead of print, 2020 Aug 14]. Clin Cancer Res. 2020;clincanres.1727.2020. doi:10.1158/1078-0432.CCR-20-1727. 

4. Lee SC, Shimasaki N, Lim JSJ, Wong A, Yadav K, Yong WP, Tan LK, Koh LP, Poon MLM, Tan SH, Ow SGW, Bharwani L, Yap YS, Foo MZQ, Coustan-Smith E, Sundar R, Tan HL, Chong WQ, Kumarakulasinghe NB, Lieow JLM, Koe PJX, Goh BC, Campana D. Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers. Clin Cancer Res. 2020;26(17):4494-4502. doi:10.1158/1078-0432.CCR-20-0768. 

5. Chin TM, Boopathy GTK, Man EPS, Clohessy JG, Csizmadia E, Quinlan MP, Putti T, Wan SC, Xie C, Ali A, Wai FC, Ong YS, Goh BC, Settleman J, Hong W, Levantini E, Tenen DG. Targeting microtubules sensitizes drug resistant lung cancer cells to lysosomal pathway inhibitors. Theranostics. 2020;10(6):2727?2743. Published 2020 Feb 3. doi:10.7150/thno.38729.

6. Kong LR, Ong RW, Tan TZ, Mohamed Salleh NAB, Thangavelu M, Chan JV, Koh LYJ, Periyasamy G, Lau JA, Le TBU, Wang L, Lee M, Kannan S, Verma CS, Lim CM, Chng WJ, Lane DP, Venkitaraman A, Hung HT, Cheok CF, Goh BC. Targeting codon 158 p53-mutant cancers via the induction of p53 acetylation. Nat Commun. 2020;11(1):2086. Published 2020 Apr 29. doi:10.1038/s41467-020-15608-y.

7. Kong LR, Mohamed Salleh NAB, Ong RW, Tan TZ, Syn NL, Goh RM, Fhu CW, Tan DSW, Iyer NG, Kannan S, Verma CS, Lim YC, Soo R, Ho J, Huang Y, Lim JSJ, Yan BJ, Nga ME, Lim SG, Koeffler HP, Lee SC, Kappei D, Hung HT, Goh BC. A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma. Nat Commun. 2020;11(1):1556. Published 2020 Mar 25. doi:10.1038/s41467-020-15318-5. 

8. Hellmann MD, Kim TW, Lee CB, Goh BC, Miller WH, Oh DY, Jamal R, Chee CE, Chow LQM, Gainor JF, Desai J, Solomon BJ, Das Thakur M, Pitcher B, Foster P, Hernandez G, Wongchenko MJ, Cha E, Bang YJ, Siu LL, Bendell J. Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors. Ann Oncol. 2019 30(7):1134-1142. 

9. Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: An international, multicenter study of the Mayo Phase 2 Consortium (NCI-9742). J Clin Oncol 2018; 36(14):1412.

10. Chen Y, Xu L, Mayakonda A, Huang ML, Kanojia D, Tan TZ, Dakle P, Lin RY, Ke XY, Said JW, Chen J, Gery S, Ding LW, Jiang YY, Pang A, Puhaindran ME, Goh BC, Koeffler HP. Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma. Nat Commun. 2019 Mar 22;10(1):1353.