When it comes to cancer, no two patients are the same. To improve the understanding, diagnosis, and treatment of cancer cases, the underlying pathology as well as patient-specific cellular or molecular biology must be considered. This is what drives Professor Chng Wee Joo from NUS Yong Loo Lin School of Medicine, and the National University Cancer Institute, Singapore (NCIS).
His lab has been at the forefront of genomics research in blood cancer over the last decade. In the case of multiple myeloma (MM), an incurable type of blood cancer, Prof Chng led a study on developing more effective treatments for ultra-high-risk MM patients.
Typically, the deletion of chromosome 17p13 and the gain of chromosome 1q21 are independent high-risk biomarkers. In ultra-high-risk groups, there is a co-occurrence of both chromosomal abnormalities.
Prof Chng and his team found that the cells of ultra-high-risk patients showed defective DNA damage response (DDR), associated with high genomic instability and persistent activation of Chk1 pathway. This finding presents the biological and therapeutic relevance of Chk1 inhibition in targeting DDR and genomic instability, and suggests that Chk1 inhibitors could be a standard of care and targeted treatment for this ultra-high-risk group.
Prof Chng was also behind the research that revealed a link between RNA defects and MM progression. Traditionally, studies had focused on the role of DNA abnormalities. He was the first Asian recipient of the Brian G.M. Durie Outstanding Achievement Award in 2020 for his research on myeloma.
As leader of the Haematologic Malignancy Tumour Group at NCIS, Prof Chng manages a translational research programme with a focus on MM, acute myeloid leukaemia and lymphoma. He is using global genomics methods (microarray and sequencing platforms) to identify novel prognostic markers as well as molecular abnormalities in these malignancies. These markers and abnormalities provide insights into disease pathogenesis and serve as potential targets for therapy.
Seeking to exploit vulnerabilities in cancer development pathways to revolutionise treatment strategies for high-risk myeloma
Specific combination of oncogenes was found to support cancer growth and survival, resulting in unfavourable treatment outcome
Researchers have discovered that a transcription factor, TOX2, was aberrantly increased in patients with Natural killer/T-cell lymphoma (NKTL), which presents a potential novel therapeutic target to treat NKTL
Soekojo, C. Y., Chung, T. H., Furqan, M. S., & Chng, W. J. (2022). Genomic characterization of functional high-risk multiple myeloma patients. Blood cancer journal, 12(1), 1-9.
Teoh, P. J., An, O., Chung, T. H., Vaiyapuri, T., Raju, A., Hoppe, M. M., ... & Chng, W. J. (2022). p53-NEIL1 co-abnormalities induce genomic instability and promote synthetic lethality with Chk1 inhibition in multiple myeloma having concomitant 17p13 (del) and 1q21 (gain). Oncogene, 41(14), 2106-2121.
Yang, F., Feng, W., Wang, H., Wang, L., Liu, X., Wang, R., ... & Zheng, G. (2020). Monocyte-derived leukemia-associated macrophages facilitate extramedullary distribution of T-cell acute lymphoblastic leukemia cells. Cancer Research, 80(17), 3677-3691.
Chong, P. S., Zhou, J., Lim, J. S., Hee, Y. T., Chooi, J. Y., Chung, T. H., ... & Chng, W. J. (2019). IL6 Promotes a STAT3-PRL3 Feedforward Loop via SHP2 Repression in Multiple MyelomaPRL-3 Activates STAT3 in Multiple Myeloma. Cancer research, 79(18), 4679-4688.
Teoh, P. J., An, O., Chung, T. H., Chooi, J. Y., Toh, S. H., Fan, S., ... & Chng, W. J. (2018). Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis. Blood, The Journal of the American Society of Hematology, 132(12), 1304-1317.
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