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Molecular Carcinogenesis

​Research head:​Professor Kanaga SABAPATHY
​Research team:

​Dr Derrick CHIA
Dr Dan LI
Dr Chao WANG
Kamaliyah Binte ABDULLAH
Kai Ning CHEW

The Sabapathy lab is focused on understanding the mechanistic basis of cancer development and resistance to therapeutic drugs, and translating the findings to generate effective therapies for cancer. To this end, multiple, nationally funded projects are undertaken by the team, as described:


Based on our expertise in generating and analysing genetically modified mice, we have been focusing on: 1) Understanding the development of liver cancers, especially those that arise in conjunction with hepatitis B virus, so as to identify biomarkers for early detection, and altered molecular pathways for therapeutic targeting; 2) Generating mouse models to recapitulate the development of liposarcomas for testing novel treatment modalities; and 3) understanding the cellular basis of breast cancer development, with a particular focus on the role of the stromal microenvironment in contributing to breast neoplasms. The use of mouse as a model organism has provided us with significant advantages in our understanding of multiple cancer types.


p53 is the most commonly mutated gene in cancers, with over 50% of cancers expressing a mutant p53, which promotes cancer development and metastasis. However, due to enormous technical difficulties, there are currently no therapies available to target mutant p53. Our efforts over the years have led to the characterisation of the various p53 mutants identified in humans, which has led to the concept of the “rainbow of p53 mutants” (Figure 1), all of which display varying degrees of oncogenic potential. Based on this concept, we have developed novel, first-in-class mutation-specific antibodies that are useful in the clinical diagnosis of mutants. We are working towards utilising these antibodies, as well as mutation-specific siRNAs, to target mutant p53 to improve treatment. Similar work is also underway to understand the functions of p73, the homologue of p53, to target its oncogenic functions in tumours.

Figure 1: “Rainbow of p53 mutants”. This "rainbow” is based on the capacity of p53 mutants to differentially transactivate target genes when expressed on a p53-null background, except in the case of DBD-DN mutants, which relates to the heterozygous state. WT and mutant p53 monomers are represented in yellow and red, respectively. PF, partial function; p53RE, p53 response element; TFRE, transcription-factor response element.

Selected publications:

  1. Dulloo I, Phang BH, Othman R, et al. Hypoxia-inducible TAp73 regulates the angiogenic transcriptome and supports tumorigenesis. Nat Cell Biol. 2015;17:511–523.
  2. Phang BH, Othman R, Bougeard G, et al. Amino-terminal p53 mutations lead to expression of apoptosis proficient p47 and prognosticate better survival, but predispose to tumorigenesis. Proc Natl Acad Sci U S A. 2015;112:E6349–E6358.
  3. Sabapathy K and Lane DP. p53: all mutants are equal, but some mutants are more equal than others – therapeutic considerations for targeting mutant p53. Nat Rev Clin Oncol. 2018;15:13–30.
  4. Hwang LA, Phang BH, Liew OW, et al. Novel tools for precision medicine– monoclonal antibodies against specific p53 hot-spot mutants. Cell Rep. 2018;22:299–312.
  5. Ubby I, Krueger C, Rosato R, et al.  Cancer therapeutic targeting using mutant-p53-specific siRNAs. Oncogene. 2019; 38:3415-3427.