Research

We identify bottlenecks in cancer signalling pathways and design new therapeutic targets -focusing on DNA damage and metabolic pathways.

Area 1

Molecular Vulnerabilities in Cancer

We identify molecular vulnerabilities in cancers by studying DNA damage response networks and cellular metabolism. Our work has uncovered non-canonical functions of the p53 tumour suppressor in safeguarding DNA replication, including how p53 prevents transcription-replication conflicts and how a p53-dependent NRF2-PARP1 axis links redox metabolism to genome integrity. Through high-throughput screens, we have identified metabolic vulnerabilities in p53-deficient cancers that can be exploited therapeutically.

Graphical abstract -p53-dependent crosstalk between DNA replication integrity and redox metabolism via NRF2-PARP1 axis (Elfar et al., NAR 2024)

Key Publications

Elfar et al., Nucleic Acids Research (2024) -NRF2-PARP1 axis
Aning & Cheok, J. Mol. Cell Biol. (2019) -drugging in the absence of p53
Kumar et al., Nature Communications (2018) -mitochondrial uncoupling in p53-defective cancers
Kumar & Cheok, Scientific Reports (2017) -RIF1 SUMOylation and genomic stability
Yeo et al., Cell Reports (2016) -transcription-replication conflicts

Area 2

Novel Therapeutics

We develop novel therapeutics through in silico and structure-activity relationship (SAR) studies. Our approach combines computational drug discovery with experimental validation, including drug repurposing strategies and combination therapies that exploit synthetic lethal interactions in cancer cells. We have demonstrated the potential of targeting multiple cancer signalling nodes -including p53 reactivation, NF-κB pathway inhibition, and cell-cycle kinase modulation -to selectively kill cancer cells while sparing normal tissue.

Graphical abstract - p53 maintains genomic stability by preventing transcription-replication conflicts, with synthetic lethality via TOP2 poisons (Yeo et al., Cell Reports 2016)

Key Publications

Yeo et al., Cell Reports (2016) -synthetic lethality via TOP2 poisons in p53-deficient cancers
Ngai et al., Int. J. Mol. Sci. (2021) -nitro-deficient niclosamide SAR study
Kong et al., Nature Communications (2020) -targeting codon 158 p53-mutant cancers
Cheok et al., Nature Reviews Clinical Oncology (2011) -translating p53 to the clinic
Cheok et al., Cell Death & Differentiation (2010) -nutlin + VX-680 combination

Area 3

Molecular Signatures & Drug Response

We identify molecular signatures that predict drug response through gene network analysis. By integrating genomics, transcriptomics, and computational approaches, we aim to understand why certain tumours respond to specific therapies and to develop predictive biomarkers that can guide treatment decisions. This work bridges fundamental cancer biology with clinical application, enabling more precise and personalised therapeutic strategies.

Key Publications

Goh et al., Int. J. Mol. Sci. (2025) -molecular cues in endometriosis and ovarian cancer
Cheok, Cell Cycle (2012) -protecting normal cells from chemotherapy

Our Approach & Technical Expertise

High-Throughput Screens

Drug and RNAi screens to identify molecular vulnerabilities in cancer cells at scale.

In Silico & SAR Studies

Computational drug discovery and structure-activity relationship studies for novel therapeutic development.

Genomics & Sequencing

Next-generation sequencing and multi-omics integration to dissect signalling pathway defects.

Animal Models

In vivo validation of therapeutic strategies using preclinical mouse models of cancer.

Specialist Capabilities

Single-molecule DNA fiber labeling for tracking of DNA replication ex vivo and in vivo

Study of Mitochondrial Superoxide/reactive oxygen species and cellular ROS status

Study of calcium fluxes in cells using live cell imaging and molecular inhibitors/activators

Monitoring of mitochondrial and cellular respiration