Fact and Figures
Oral cancer is a type of head and neck cancer. Although relatively rare, oral cancer is the third most common cancer among Malaysian Indian community in Malaysian Ministry of Health Hospitals. Oral cancer is the sixth most common cancer in the world and is highly associated with the practice of tobacco smoking, betel quid chewing and excessive alcohol consumption.
More recently however, for reasons that are still unclear, oral cancer is increasingly being diagnosed in individuals who do not practice these risk habits. Although oral cancer can be fairly easily detected, death rates are higher than for many other cancer types mainly because it is often presented late.
- National Cancer Registry, Ministry of Health (Malaysia). Malaysia Cancer Incidence Report 2003-2005. Kuala Lampur, Malaysia: National Cancer Registry, Ministry of Health (Malaysia), 2008.
More than a quarter of a million individuals are diagnosed with oral cancer annually and two thirds of these are diagnosed in developing countries, with the highest incidence in South and South East Asia. Unfortunately, 50% of oral cancer patients die within 5 years of their diagnosis and those who have been successfully treated need to cope with the devastating consequences of their treatment involving their appearance and function.
While the poor survival rate of oral cancer reflect late diagnosis, this is also attributed to our poor understanding of how this cancer is initiated or developed. The aim of the Oral Cancer Research Team program is to obtain a comprehensive understanding of the genes that cause oral cancer development, and to use this as a basis to develop molecular tools for early detection and treatment. We are working towards targeted therapy to effective treat the tumour and avoid harming normal cells. Find out more below:
- Oral Cancer Genes
- Oral Cancer Models
- Targeting Oral Cancer
- Oral Cancer Awareness
- Scientific Publications
One of the biggest challenges in oral cancer research is that we still know little about genes that drive cancer development and we do not know enough about how to kill cancers.
Cancers can be caused by the genetic changes in cells. When those particular genetic changes are identified, novel drugs can be developed for cancer treatment. The use of such drugs, also referred as targeted therapy, kills cancer cells specifically and therefore works effectively without harming normal cells in our body. Notably, targeted therapy has been used successfully to treat some types of cancers.
- However, the majority of these drugs have been developed only against breast cancer, colon cancer and lymphomas, and there remains a gap in the development of targeted therapy particularly against “Asian Cancers” such as oral cancer. Hence, the identification of genetic changes specific to oral cancer cells is very crucial because it affords an opportunity to use this information for the development of drugs to treat this disease.
- Our ability to catalogue the genome to unprecedented detail affords an opportunity for us to identify genetic alterations in tumor cells. The over-arching aim of this research area is to understand the molecular basis of oral cancer with an emphasis to use this information for the development of tools to complement clinical management of oral cancer.
We have used genomic analyses to characterize the cancer genome and to identify genes that are expressed exclusively in oral cancer and not in normal tissues. Some of these genes provide a survival advantage to cancer cells therefore, providing an opportunity to target them for therapeutic purposes.
- More recently, we have focused our efforts in detecting early genetic events that drive transformation. Oral cancer affords an ideal model to understand early and possible tumour initiating events as oral potentially malignant disorders (OPMD) clearly precedes the development of oral squamous cell carcinoma (OSCC). Unlike OSCC where genetic alterations are no longer reversible and treatment options are limited, OPMDs provide a window of opportunity to intervene before the development of occult tumors.
- However, only 4% of OPMDs will progress to become OSCC in 20 years, therefore identifying which lesions will transform is crucial in managing these patients. A good understanding of which genes or pathways drive malignant transformation affords us the opportunity to use these as biomarkers or targets for therapeutic intervention.
- Collectively, the use of gene signatures will help manage patients better by identifying high risk individuals early and ensuring that they receive appropriate treatments. “If my GP and I had known that the ulcers would become cancerous, I would have saved precious time for treatment,” said Harun, oral cancer survivor.
- CURRENT PROJECTS
- 1. The use of next generation sequencing to map evolutionary events in oral cancer development
- 2. Defining tumour boundaries using biological markers
- 3. Clinical validation of a 4-protein signature for identifying patients with lymph node metastasis
- Reference: Mehanna, H. M., Rattay, T., Smith, J. and McConkey, C. C., Treatment and follow-up of oral dysplasia – a systematic review and meta-analysis, Head Neck, 2009.
The development of biomarkers for diagnosis and treatment of cancer requires an understanding of how these genes cause cancer. Cancer Research Malaysia has established the largest panel of Asian oral cancer cell lines. These cancer cell lines are essential because the development of biomarkers for diagnosis and treatment of cancer requires a model to understand how cancer genes cause cancer.
- In fact, these cell lines were developed from Malaysian patients and thus make good models to study oral cancer in the laboratory. In addition, a complete understanding of cancer development also requires animal models of cancer. Animal models are important in developing and testing novel drugs for cancer treatment and are crucial to ensure that the biomarkers and therapeutic targets that we work on can be developed further to benefit our patients.
All of our oral cancer cell lines have been authenticated to their respective patient tissue samples. We have detailed information regarding the growth rate, migration and invasion potential, sensitivity to UV irradiation and ability to form tumours in animals. We are able to induce oral cancer in animal model according to the origin of the cancer which serves as an excellence model to know the cancer better and provided a model for anti-cancer drug testing.
In the last 8 years we have developed and refined methods of culturing primary cultures from OSCC and normal oral mucosa tissues (Hamid et al. 2007). The cell lines that were developed at Cancer Research Malaysia are spontaneously immortalized, and molecular analyses demonstrate that they represent OSCC tissue specimens closely. These cell lines and their use in vivo have been used routinely to study gene function and to identify new therapies for OSCC, and have also been utilized by other laboratories in Malaysia, USA, India, Thailand and Taiwan to improve our understanding of OSCC development.
- Recently, we have extended our work in developing OSCC models to the development of primary cultures for oral potentially malignant disorders (OPMD). Worldwide there are currently only 24 existing primary cultures of OPMD and we hope to add to these to represent the heterogeneity within these lesions. We anticipate that these cell lines will help to improve our understanding of oral cancer development particularly in the crucial events that drive malignant transformation.
- CURRENT PROJECTS
- 1. The use of in vitro and in vivo models for modelling drug sensitivity
- 2. The development of oral potentially malignant models
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To request for oral cancer cell lines that were developed at Cancer Research Malaysia, please send your enquiries to email@example.com.
Current treatments are still incomplete cures, in part because patients present late, but also because tumour recurrences and secondary tumours are common in oral cancer and these are more difficult to treat. On top of that, current treatments cause many side effects and lead to a poor quality of life. Hence, the development of targeted therapy is vital to make up for the shortfalls of the current treatments.
Our research to develop new therapies for oral cancer is divided into 2 areas. The first is to activate the immune system in oral cancer patients to fight cancer. The second area is to identify new and existing drugs for the treatment of oral cancer based on genetic signatures.
- CURRENT PROJECTS
- 1. The development of peptide vaccines against oral cancer specific antigens
- 2. Modelling drug sensitivity through gene expression signatures
- “We are grateful to all consented patients and volunteers who have participated in our research and acknowledge the excellent clinical and scientific input from our collaborators including The Oral Cancer Research and Co-ordinating Centre (OCRCC), University Malaya (UM) and the Oral Health Division of the Ministry of Health, Malaysia.
- We also have many other partners for the various projects that we conduct including the National Institutes of Health, USA, Queen Mary School of Medicine and Dentistry, UK, University of Colorado, USA and the Uniform Services University of the Health Sciences, USA, amongst others,” said Prof Dr Cheong Sok Ching, Group Leader for Oral Cancer Research Programme.,” said Prof Dr Cheong Sok Ching, Group Leader for Oral Cancer Research Programme.
Despite the easy accessibility of oral cavity for examination to detect early signs of oral cancer, oral cancer patients in Malaysia often present at very late stages where the cancer has spread beyond the mouth, making ideal clinical management impossible.
“Sometimes A Big Mouth Is A Good Thing” campaign by Cancer Research Malaysia seeks to increase awareness and discussion about oral cancer. The phrase is coined not only to prompt the public to open their mouths to check for oral cancer but also equally important to raise awareness of the disease by encouraging public to talk about oral cancer in the community.
Partnering with the Malaysian Dental Association (MDA), Canser Research Malaysia’s recent study involving 400 local dentists showed that the majority of dental practitioners in Malaysia are keen to be involved in the prevention and early detection of oral cancer campaign.
- Based on this study, we have launched the “Be Frank: Dentist Programme” where private dental practitioners come forward and participate in programme to promote early detection and prevention of oral cancer. We have trained 21 dentists to identify pre-cancerous oral lesion and to encourage patients at their clinics the importance of oral cancer screening and early detection. To date, through this dentists, the programme has reached 1,400 individuals.
- TAKE ACTION!
Run the “Sometimes a Big Mouth is a Good Thing” programme in your clinic by displaying information about oral cancer and conducting mouth cancer examination on your clients. We are calling out to all private dental practitioners to join us in our crusade to fight cancer! Contact Nabihah Haron at firstname.lastname@example.org or +603 5639 1874 for more information.
- “Malaysia has 4,300 practising dentists and at least 30% of the Malaysian population visit their dentists regularly. Therefore, dentists are in a unique position to promote oral cancer awareness and early detection of oral cancer. The MDA is committed to improve oral cancer survival through prevention and early detection and is very happy to partner with Cancer Research Malaysia in their education and outreach programmes,” said Dr Haja Badrudeen, former President of Malaysian Dental Association.
- 1. “Co-expression of TWIST1 and ZEB2 in oral squamous cell carcinoma is associated with poor survival.” Y.K. Kong, S.N. Syed Zanaruddin, S.H. Lau, A. Ramanathan, T.G. Kallarakkal, V.K. Vincent-Chong, W.M. Wan Mustafa, M.T. Abraham, Z.A. Abdul Rahman, R.B. Zain & S.C. CheongPLoS One. 2015 Jul 27;10(7):e0134045.doi: 10.1371/journal.pone.0134045.
- 2. “ERG oncoprotein expression in prostate carcinoma of different ethnicities.” G.M. Kelly, Y.H. Kong, A. Dobi, S. Srivastava, I.A. Sesterhenn, R. Pathmanathan, H.M. Tan, S.H. Tan & S.C. CheongMolClinOncol. 2015 Jan;3(1):23-30.
- 3. “Heterotrimeric G-protein alpha-12 (Gα12) subunitpromotes oral cancermetastasis.” C.P. Gan, V. Patel, C.M. Mikelis, R.B. Zain, A.A. Molinolo, M.T. Abraham, S.-H. Teo, Z.A.A. Rahman, J. S. Gutkind&S.C. CheongOncotarget2014 Oct 30;5(20):9626-40.
- 4. “CD4+CD25hiCD127low regulatory T cells are increased in oral squamous cell carcinoma patients.”K.P. Lim, N.A.L. Chun, S.M. Ismail, M.T. Abraham, M.N. Yusoff, R.B. Zain, W.C. Ngeow, S. Ponniah& S.C. Cheong.PLoS ONE 2014 Aug 25: 9(8): e103975.doi: 10.1371/journal.pone.0103975.
- 5. “Establishing and managing a periodontal biobank for research: the sharing of experience.”R.D. Vaithilingam, S.H. Safii, N.A. Baharuddin, L.P. Karen-Ng, R. Saub, F. Ariffin, H. Ramli, A. Sharifuddin, M.F.H. Hidayat, R. Raman, Y.K. Chan, N.A. Rani, R.A. Rahim, S.C. Cheong, P.M. Bartold& R.B. Zain. Oral Diseases 2014 June 13. doi: 10.1111/odi.12267.
- 6. “Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy.” K.P. Lim, N.A.L.Chun, C.P. Gan, S.H. Teo, Z. A. Abdul Rahman, M.T. Abraham, R.B. Zain, S. Ponniah & S.C. Cheong. Hum Vaccin Immunother. 2014 Jul 7;10(11).
- 7. “Dentists’ Perception of the Role they Play in Early Detection of Oral Cancer.” Amyza Saleh, Yink Heay Kong, Nedunchelian Vengu, Haja Badrudeen, Rosnah Binti Zain, Sok Ching Cheong. Asian Pac J Cancer Prev. 2014;15(1):229-37.
- 8. “Comparative proteomics analysis of oral cancer cell lines: identification of cancer associated proteins.” Karsani SA, Saihen NA, Zain RB, Cheong SC,Abdul Rahman M. Proteome Sci. 2014 Jan 15;12(1):3.
- 9. “Potentially malignant disorders of the oral cavity: current practice and future directions in the clinic and laboratory.” K.R. Dionne, S. Warnakulasuriya, R.B. Zain, S.C.Cheong. Int J Cancer. 2014 Jan 31. doi: 10.1002/ijc.28754).
- 10. “Moving into a new era of periondontal genetic studies: relevance of large case-control samples of severe phenotypes for genome wide association studies.” R.D. Vaithilingam, S.H. Saifi, N.A. Baharuddin, C.C. Ng, S.C. Cheong, P.M. Bartold, A.S. Schaefer, B.G. Loos. Journal of Periondontal Research 2014 Feb 17. doi: 10.1111/jre.12167.
- 11. “Seropositivity of HPV 16 E6 and E7 and the risk of oral cancer in Malaysia.” G.R. Wong, K.O. Ha, W.H. Himratul-Aznita, Y.-H. Yang, W.M. Wan Mustaffa, K.M. Yuen, M.T. Abraham, K.K. Tay, L.P. Karen-Ng, R.Saini, S.C. Cheong, R.B. Zain. Oral Diseases 2013 Dec 9. doi: 10.1111/odi.12218.
- 12. “Genome Wide Analysis of Chromosomal Alterations in Oral Squamous Cell Carcinomas Revealed Over Expression of MGAM and ADAM9”. V.K. Vincent-Chong, A.Anwar, L.P. Karen-Ng1, S.C. Cheong, Y.-H. Yang, P.J. Pradeep, Z.A.A. Rahman, S.M. Ismail, Z.M. Zaini, N. Prepageran, T.G. Kallarakkal, A. Ramanathan, Y. Hasmawati4, M.R.N. Shielawati, W.M. Wan Mustafa, M.T.Abraham, K.K, Tay, R.B. Zain. PLoS One. 2013;8(2):e54705. doi: 10.1371.
- 13. “Common oncogenic mutations are infrequent in oral squamous cell carcinoma of Asian origin.” Sharifah Nurain Syed Zanaruddin, Pei San Yee, Seen Yii Hor, Yink Heay Kong, Wan Maria Nabillah Wan Abd Ghani, Wan Mahadzir Wan Mustafa, Rosnah Binti Zain, Stephen S. Prime, Zainal Ariff Abd Rahman, Sok Ching Cheong. PLoS One. 2013 Nov 4;8(11):e80229. doi: 10.1371
- 14. “Dysregulation of miR031 and miR-375 expression associated with clinical outcomes in oral carcinoma”. M.Y. Siow, L.P. Karen-Ng, V.K. Vincent-Chong, J. Marhazlinda, M.T. Abraham, Z.A.A. Rahman, T.G. Kallarakkal, S.C. Cheong & R.B. Zain. Oral Diseases 2013 Apr 17. doi: 10.1111/odi.12118.
- 15. “Oral cancer secretome: Identification of cancer associated proteins.” Hong-Yun Chang, Seen-Yii Hor, Kue-Peng Lim, Rosnah Binti Zain, Sok-Ching Cheong, Mariati Abdul Rahman and Saiful Anuar Karsani. Electrophoresis. 2013 Aug;34(15):2199-208
- 16. “Four protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma.” S.N. Syed Zanaruddin, A. Saleh, Y.-H. Yang, S. Hamid, W.M. Wan Mustafa, A.A.N. Khairul Bariah, S.-H. Teo, R.B. Zain, S.H. Lau & S.C. Cheong. Human Pathology-2013 Mar;44(3):417-26.
- 17. “Promoting oral cancer awareness and early detection in a developing country: using a mass media approach.” A. Saleh, Y.-H. Yang, W.M.N. Wan Abd Ghani, N. Abdullah, J.G. Doss, R. Navonil, Z.A. Abdul Rahman, S.M. Ismail, N. Abu Talib, R.B. Zain, S.C. Cheong. Asian Pac J Cancer Prev 2012; 13(4)” 1217-1224.
13. “An oral cancer biobank initiative: a platform for multidisciplinary research in a developing country.” R.B. Zain, A. Vimmitra, W.M.N. Wan Abd Ghani, I.A. Razak, R.J. Raja Latifah, S.M. Ismail, A.A. Sallam, A.Z. Bustam, Z.A. Abdul Rahman, A. Hussein, N. Talib, S.C. Cheong, A. Jallaludin. Cell Tissue Bank DOI 10. 1007/s10561-012-9298-0.
- 18. “Ultrasensitive Detection of Cancer Biomarkers in the Clinic using a Nanostructured Microfluidic Array.” R. Malhotra, V. Patel, B.V. Chikkaveeraiah, B.S.Munge, S.C. Cheong, R.B. Zain, M.T. Abraham, D.K. Dey, J.S. Gutkind & J.F. Rusling. Anal Chem. 2012 Jun 14.
- 19. “MDM2 splice variants and its presence in oral cells.” K.K. Sam, C.P. Gan, P.S. Yee, C.E. Chong, K.P. Lim, K.L.P. Ng, W.S. Chang, S. Nathan, Z.A. Abdul Rahman, S.M. Ismail & S.C. Cheong. Oral Oncol. 2012 Nov;48(11):1128-35
- 20. “Increased secretion of tissue inhibitors of metalloproteinases 1 and 2 (TIMPs -1 and -2) in fibroblasts are early indictors of oral sub-mucous fibrosis and ageing.” Gayani N. Pitiyage, Kue Peng Lim, Emilios Gemenitzidis, Muy-Teck Teh, Ahmad Waseem, Stephen S. Prime, Wanninayake M. Tilakaratne, Farida Fortune, E. Kenneth Parkinson. J Oral Pathol Med. 41 (6): 454-462 (2012).
- 21. “Over-expression of MAGED4B increases cell migration and growth in oral squamous cell carcinoma and is associated with poor disease outcome.”C.E. Chong, K.P. Lim, C.P. Gan, C. A. Marsh, R.B.Zain, M.T. Abraham, S.S. Prime, S-H Teo, J.S. Gutkind, V. Patel2 & S.C. Cheong (2012). International Journal of Cancer. Cancer Letters 321 (2012): 18–26.
- 22. “Senescent mesenchymal cells accumulate in human fibrosis by a telomere-independent mechanism and ameliorate fibrosis through matrix metalloproteinases.” G.N. Pitiyage, P. Slijepcevic, A. Gabrani, Y.G. Chianea, K.P. Lim, S.S. Prime, W.M. Tilakaratne, F. Fortune and E.K. Parkinson. Journal of Pathology. 2011, 223: 604-617.
- 23. “Combined effects of isothiocyante (ITC0 intake, glutathione S-transferase (GST) polymorphisms and risk habits for age of oral squamous cell carcinoma development.” K.L.P. Ng, M. Jamaludin, Z.A.Abdul Rahman, Y.H. Yang, N. Jalil, S.C. Cheong & Zain, R.B. 2011. Asian Pac J Cancer Prev 12: 1-6.
- 24. “Valproic acid causes growth inhibition of oral cancer by inducing terminal differentiation and senescence” C.P. Gan, S. Hamid, S.Y. Hor, R.B. Zain, S.M. Ismail, W.M. Wan Mustafa, S.H. Teo, N. Saunders & S.C. Cheong.. Head and Neck Mar;34(3):344-53.
- 25. “Fibroblast gene expression profile reflects the stage of tumour progression in oral squamous cell carcinoma.” Lim KP, Cirillo N, Hassona Y, Wei W, Thurlow JK, Cheong SC, Pitiyage G, Parkinson EK, Prime SS. J Pathol. (2011) Mar;223(4):459-69.
- 26. “Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia.” Saini R, Tang TH, Zain RB, Cheong SC, Musa KI, Saini D, Ismail AR, Abraham MT, Mustafa WM, Santhanam J. J Cancer Res Clin Oncol. (2011)Feb;137(2):311-20. Epub 2010 Apr 24.
- 27. “Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples.” Saleh A, Zain RB, Hussaini H, Ng F, Tanavde V, Hamid S, Chow AT, Lim GS, Abraham MT, Teo SH, Cheong SC. Oral Oncol. (2010) May;46(5):379-86.
- 28. “Reply to “Letter to the Editor” A.Saleh, R.B. Zain, V. Tanavde, & S.C. Cheong. 2010. Oral Oncol 890-891.
- 29. “Gene expression in human oral squamous cell carcinoma is influenced by risk factor exposure.” Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, Pathmanathan R, Prime SS, Teo SH, Patel V, Gutkind JS. Oral Oncol. (2009) 45(8):712-9.
- 30. “Upregulation of FOXM1 is an early event in human squamous cell carcinoma and co-operates with nicotine in malignant transformation.” E Gemenetzidis, A Bose, AM Riaz, T Chaplin, BD Young, M Ali, D Sudgen, JK Thurlow, SC Cheong, SH Teo, H Wan, A Wasseem, AK Parkinson and MT Teh. PlosOne (2009) 4(3) e4849.
- 31. “GSTM1, GSTT1 and CYP1A1 polymorphism and risk of oral cancer: a case-control study in Jakarta population, Indonesia.” R. Amtha, S.C. Cheong, R.Zain, I. Abdul Razak, B.Basuki, B.O.Roeslan, W. Gautama & D. Purwanto. 2009. Asian Pac J Cancer Prev 10(1): 21-26.
- 32. “MDM2 SNP309 does not confer an increased risk to oral squamous cell carcinoma but may modulate the age of disease onset”. S Hamid, YH Yang, KLP Ng, SM Ismail, RB Zain, KP Lim, WM Wan Mustafa, MT Abraham, SH Teo and SC Cheong. Oral Oncol (2009) 45(6):496-500.
- 33. “Building partnership in oral cancer research in a developing country-processes and barriers.” RB Zain, WMN Ghani, IA Razak, RL Raja Jallaludin, AR Samsuddin, SC Cheong, N Abdullah, AR Ismail, N Abu Talib and A Jallaludin. Asian Pac J Cancer Prev. (2009) 10(3):513-8.
- 34. “Oral Cancer Prediction Model for Malaysian Sample.” RM Dom, SA Kareem, B Abidin, RL Raja Jallaludin, SC Cheong and RB Zain. Austral-Asian Journal of Cancer (2008) 7(4): 209-214.
- 35. “Establishment and Characterization of Asian Oral Cancer Cell lines as In Vitro Models to Study a Disease Prevalent in Asia.” S Hamid, KP Lim, RB Zain, SM Ismail, SH Lau, WMW Mustafa, MT Abraham and SC Cheong. Int J Mol Med (2007) 19(3): P453.
- 36. “HPV infection and the alterations of the pRB pathway in oral carcinogenesis”. KP Lim, S Hamid, SH Lau, SH Teo and SC Cheong Oncol Rep (2007)17: P321-1326.
- 37. “Alterations of the p14ARF-p53-MDM2 pathway in oral squamous cell carcinoma: MDM2 overexpression is a common event.” KP Lim, S Hamid, SH Lau, SH Teo and SC Cheong. Oncol Rep (2005) 14: P963-968.
- 38. “Human telomerase reverse transcriptase expression in oral carcinogenesis – A preliminary report.” S Kumar, RB Zain, SM Ismail and SC Cheong. J Exp Clin Cancer Res (2005) 24(4): P207-214.