Facts and Figures

Nasopharyngeal cancer (NPC) is a major health problem in Malaysia, being the fourth most common cancer among Malaysians and third most common cancer among Malaysian men. NPC is strongly associated with Epstein-Barr Virus (EBV) and occurs at the back of the nose. Radiotherapy is effective against early stage NPC; however, over 70% of cases presented with late stage disease, principally as a result of the non-specific symptoms and the difficulty of examining the nasopharynx clinically.

These patients often suffer from undesirable side effects of chemoradiotherapy treatments that result in poor quality of life. In addition, a subset of tumours is resistant to many forms of treatment and recurrent disease has a significant impact on survival rates. Therefore, reliable biomarkers for diagnosis, prognosis and treatment for NPC are urgently needed.

Sources:

  • Omar, Z.A. and Tamin, N.S.I., National Cancer Registry, Malaysia Cancer Statistics – Data and Figure Report 2007. Ministry of Health Malaysia, 2011.

Research Focus

Radiotherapy is effective against early stage of nasopharyngeal cancer (NPC); however, over 70% of cases presented with late stage disease, principally as a result of the non-specific symptoms and the difficulty of examining the nasopharynx clinically.

The goal of the NPC team at CARIF is scientific excellence aimed at improving our most basic understanding of the molecular mechanisms underlying disease initiation and progression, and to use this knowledge to develop markers for the early detection of NPC and novel therapeutic approaches for prevention and treatment. To this end, our goal aims to develop robust model systems of NPC pathogenesis as well as deciphering the full NPC transcriptome to learn the nature of the genes that get altered in this disease process.

Reversing the who might develop NPC in Malaysia, reversing to make NPC the least common cancer in Malaysia, reversing to make NPC easily treatable.

    • WHY?
      Although the genetic alterations in NPC have been studied for some time, current molecular models are unable to explain fully the complexity of the disease. In Cancer Research Malaysia, we have completed the first genome-wide (more than 15,000 genes) study of Malaysian NPC and identified a number of genes that appear to be important in the development of the disease. NPC cell lines are important model systems for analyzing the complex life cycle and pathogenesis of the Epstein-Barr virus (EBV) as well as for understanding the underlying molecular basis of disease development and progression.
    • WHAT?
      Further, biomarkers that can be used to predict treatment response would allow us to specifically tailor the treatment modality for the patients. While EBV infects more than 90% of the world population, its precise role in the pathogenesis of NPC remain unclear. A fuller understanding of the association between EBV and NPC will have relevance to the development of novel therapeutic approaches to target EBV that are also likely to be applicable to other EBV-related cancers.
    • HOW?
      Our goal is focused on establishing primary and permanent cultures from clinically defined NPC biopsies with the view of using these for next generation sequencing (NGS) and biochemical signalling pathway analysis. To this end, normal NPC equivalents important for comparative studies are few and limiting, and thus aim to establish normal primary cultures with the view of immortalizing them. These cells lines will represent invaluable tools and reagents for studying the molecular and biochemical basis of NPC pathogenesis. Furthermore, these cell lines are ideal to transplant orthotopically into the nasopharynx of SCID-NOD mice for understanding tumor development and progression in vivo.
    • We have been integrally involved in establishing the first Malaysian NPC Biospecimen Network and NPC Society of Malaysia, together with seven academic institutions and hospitals across Malaysia. On behalf of the Malaysian NPC Study Group, we have evaluated the clinical value of plasma EBV DNA load in the largest cohort of Malaysian patients with NPC.
    • CURRENT PROJECTS
    • + Deciphering the complex architecture of the NPC genome with the clear objective of improving our most basic understanding of NPC pathogenesis.
    • + To develop markers of disease progression and novel therapeutic approaches for NPC.
    • + Develop peptide vaccine as treatment option for NPC
    • 1. HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese.” Chin YM, Mushiroda T, Takahashi A, Kubo M, Krishnan G, Yap LF, Teo SH,
      Lim PV, Yap YY, Pua KC, Kamatani N, Nakamura Y, Sam CK, Khoo AS; Malaysian NPC Study Group, Ng CC. Int J Cancer. (2015) Feb 1;136(3):678-87.
    • 2. “Oncogenic effects of WNT5A in Epstein-Barr virus‑associated nasopharyngeal carcinoma.” Yap LF, Ahmad M, Zabidi MM, Chu TL, Chai SJ, Lee HM, Lim PV, Wei W, Dawson C, Teo SH, Khoo AS, Int J Oncol. (2014) May;44(5):1774-80. doi: 10.3892/ijo.2014.2342. Epub 2014 Mar 13.
    • 3. “Clinical significance of plasma Epstein-Barr Virus DNA loads in a large cohort of Malaysian patients with nasopharyngeal carcinoma.” Chai SJ, Pua KC, Saleh A, Yap YY, Lim PV, Subramaniam SK, Lum CL, Krishnan G, Wan Mahiyuddin WR; the Malaysian NPC Study Group, Teo SH, Khoo AS, Yap LF. J Clin Virol. (2012) Sep;55(1):34-39. Epub 2012 Jun 26.
    • 4. “Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese.”  Yew PY, Mushiroda T, Kiyotani K, Govindasamy GK, Yap LF, Teo SH, Lim PV, Govindaraju S, Ratnavelu K, Sam CK, Yap YY, Khoo AS, Pua KC, Nakamura Y; The Malaysian NPC Study Group, Ng CC. Mol Carcinog. (2011) Dec 27. doi: 10.1002/mc.21857. [Epub ahead of print]
    • 5. “A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma.” Ng CC, Yew PY, Puah SM, Krishnan G, Yap LF, Teo SH, Lim PV, Govindaraju S, Ratnavelu K, Sam CK, Takahashi A, Kubo M, Kamatani N, Nakamura Y, Mushiroda T. J Hum Genet. (2009) 54(7):392-7.
    • 6. “The ATM tumor suppressor gene is downregulated in EBV-associated nasopharyngeal carcinoma.” S Bose*, LF Yap*, M Fung, J  Starzcynski, A Saleh, S Morgan, CW Dawson, MB Chukwuma, E Maina, Buettner M, W Wei, J Arrand, PVH Lim, LS Young, SH Teo,T Stankovic, CBJ Woodmanand PG  Murray. J Pathol (2009) 217: 345–352.
    • 7. “Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin’s lymphoma cells mediates Up-regulation of CCL20 and the migration of regulatory T cells.” KRN Baumforth, A Birgersdotter, GM Reynolds, W Wei, G Kapatai, JR Flavell, E Kalk, K Piper, S Lee, L. Machado, K Hadley, A. Sundblad, J  Sjoberg, M Bjorkholm, A.A Porwit, LF Yap, SH Teo, RG Grundy, LS Young, I Ernberg, CBJ Woodman and PG  Murray. Am J Pathol. (2008) 173(1):195-204.
    • 8. “Nasopharyngeal Carcinoma Database.” Pua KC, Khoo AS, Yap YY, Subramaniam SK, Ong CA, Gopala Krishnan G, Shahid H; Malaysian Nasopharyngeal Carcinoma Study Group. Med J Malaysia. (2008) Sep;63 Suppl C:59-62. (SH Teo and LF Yap are members of The Malaysian Nasopharyngeal Study Group)
    • 9. “Malaysian Nasopharyngeal Study Group” KC Pua,  ASB Khoo, YY Yap,  SK Subramaniam, C.A Ong, G Gopala Krishnan, H Shahid, The Malaysian NPC Study Group. Nasopharyngeal carcinoma database. Med J Malaysia. 63 (2008) (Suppl C): 59-62. (SH Teo and LF Yap are members of The Malaysian Nasopharyngeal Study Group)