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. Winnie Yeo, Hyun Cheol Chung, Stephen L. Chan, Lingzhi Z. Wang, Robert Lim, Joel Picus, Michael Boyer, Frankie K.F. Mo, Jane Koh, Sun Y. Rha, Edwin P. Hui, Hei C. Jeung, Jae K. Roh, Simon C.H. Yu, Ka F. To, Qian Tao, Brigette B. Ma, Anthony W.H. Chan, Joanna H.M. Tong, Charles Erlichman, Anthony T.C. Chan, and Boon C. Goh. Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of the Mayo Phase II Consortium and the Cancer Therapeutics Research Group. J Clin Oncol 2012;30(27):3361-7.

2. BC Goh, Reddy NJ, Dandamudi U, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD. An Evaluation of the Drug Interaction Potential of Pazopanib, Using a Modified Cooperstown 5+1 Cocktail in Patients with Advanced Solid Tumors. Clin Pharmacol Ther 2010;88(5):652-9.

3. Chiung-Ing Wong, Tong-San Koh, Ross Soo, Septian Hartono, Choon-Hua Thng, Evelyn McKeegan, Wei-Peng Yong, Chien-Shing Chen, Soo-Chin Lee, John Wong, Robert Lim, Norita Sukri, Siew-Eng Lim, Ai-Bee Ong, Joyce Steinberg, Neeraj Gupta, Rajendra Pradhan, Rod Humerickhouse, Boon-Cher Goh. Phase I and biomarker study of ABT-869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies. J Clin Oncol 2009;27(28):4718.

4. Wen-Son Hsieh, Ross Soo, Bee-Keow Peh,Thomas Loh, Difeng Dong, Donny Soh, Lim-Soon Wong, Simon Green, Judy Chiao, Chun-Ying Cui, Yoke-Fong Lai, Soo-Chin Lee, Benjamin Mow, Richie Soong, Manuel Salto-Tellez, Boon-Cher Goh. Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer. Clin Cancer Res 2009;15(4):1435-42.

5. Tham LS, Goh BC, Nafziger A, Guo JY, Wang LZ, Soong R, Lee SC. A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9. Clin Pharmacol Ther 2006;80(4):346-455.

6. Soo-Chin Lee, Swee-Siang Ng, Johannes Oldenburg, Pei-Yi Chong, Simone Rost, Jia-Yi Guo, Hui-Ling Yap, Sheila Clare Rankin, Hui-Boon Khor, Tiong-Cheng Yeo, Kheng-Siang Ng, Richie Soong, Boon-Cher Goh. Inter-ethnic variability of warfarin maintenance requirement is explained by vkorc1 genotype in an Asian population. Clin Pharmacol Ther 2006;79(3):197-205.

7. Anthony T.C. Chan, Mow-Ming Hsu, Boon C. Goh, Edwin P. Hui, Tsang-Wu Liu, Michael J. Millward, Ruey-Long Hong, Jacqueline Whang-Peng, Brigette B.Y. Ma, Ka F. To, Matthias Mueser, Nadia Amellal, Xiao Lin, Alex Y. Chang. A multi-center, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol 2005;23(15):3568-76.

8. Feng ZHAO, Celine LOKE, Sheila Clare RANKIN,Jia-Yi GUO, How Sung LEE, Tuck Seng WU, Theresa TAN, Te-Chih LIU, Wan-Liang LU, Yean-Teng LIM, Qiang ZHANG, Boon Cher GOH, Soo Chin LEE. Novel CYP2C9 genetic variants in Asians and their influence on maintenance warfarin dose. Clin Pharmacol Ther 2004;76:210.

9 Boon-Cher Goh, Soo-Chin Lee, Ling-Zhi Wang, Lu Fan, Jia-Yi Guo, Jatinder Lamba, Erin Schuetz, Robert Lim, Hong-Liang Lim, Ai-Bee Ong, How-Sung Lee. Explaining inter-individual variability of docetaxel pharmacokinetics and pharmacodynamics in asians through phenotyping and genotyping strategies. J Clin Oncol 2002;20:3683-3690.

10. Goh BC, Ratain MJ, Smith R, Bertucci D, Mani S, Vogelzang NJ, et al. Phase I study of ZD9331 using a 5-day short infusion schedule. J Clin Oncol 2001;19:1476-1484