Researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) have identified a ‘master switch’ responsible for driving tumour growth in an aggressive form of breast cancer. Blocking the switch with a targeted drug was also found to reduce cancer cell growth and reduce its spread.
One of the deadliest forms of breast cancer, Triple-negative breast cancer (TNBC) accounts for approximately 15 to 20 per cent of breast cancers and is associated with a high risk of early recurrence, metastasis and poor survival [1] . As TNBC is highly aggressive and lacks effective targeted therapies, a small population of cancer stem cells often resist treatment and fuels tumour regrowth in patients—leading to rapid metastasis and recurrence. Investigating the mechanisms that allow these cancer cells to survive, spread and resist therapy, the research team homed in on regulators of a key pathway driving TNBC known as Wnt signalling.
The research team identified a previously unknown master regulator, DP103, which creates a self-reinforcing cycle that keeps cancer cells growing, spreading and resisting treatment while maintaining the population of cancer stem cells responsible for disease recurrence. Following the discovery, the team further evaluated if an investigational targeted drug, RX-5902 (Supinoxin), could turn off this ‘master switch’ and block its effects in driving TNBC.
Published in Cell Death and Disease , the study combined advanced molecular biology with state-of-the-art laboratory models, analysing patient-derived datasets, human breast cancer cells, and three-dimensional tumour models that better mimic how cancers grow in the body. The findings were then validated in laboratory models and human tumour organoids to determine whether blocking this pathway could slow cancer progression. Analysing 21 samples, the team found that the drug reduced cancer stem cell viability by 40 to 60 per cent. Tumour growth in the laboratory-grown tumour models also fell by about 50 per cent. In laboratory models, the treatment reduced tumour size by around 90 per cent while largely sparing healthy cells. It also extended survival, with 50 per cent of treated models reaching 70 days and beyond, compared to none in the untreated group.
Research Assistant Professor Alan Prem Kumar from the NUS Centre for Cancer Research (N2CR) and Department of Pharmacology, NUS Medicine, who is Principal Investigator of the study, said, “Patients with triple-negative breast cancer are facing an aggressive form of breast cancer with limited treatment options. Our findings suggest that DP103 could potentially serve as a diagnostic biomarker to identify the patients most likely to benefit from RX-5902 treatment, paving the way for a more precise, personalised approach to treating triple-negative breast cancer. Instead of treating all patients the same, future clinical trials could focus on those whose tumours have high levels of DP103, where the therapy is expected to have the greatest impact.”
Dr Cai Wanpei, the first author of the study, who was a PhD student at the N2CR and Department of Pharmacology, NUS Medicine, during the time of the study, added, “The RX-5902 drug is a first-in-class oral targeted therapy designed to block a key cancer-promoting pathway known as Wnt/β-catenin. By preventing β-catenin from entering the cell nucleus, the drug switches off genes that drive cancer growth, spread and survival. This slows tumour progression and triggers apoptosis—the natural death of cancer cells.”
The research team involved collaborators from the NUS Cancer Science Institute of Singapore, Duke-NUS Medical School, Nanyang Technological University, National Cancer Centre Singapore, Singapore General Hospital, Agency for Science, Technology and Research, Rexahn Pharmaceuticals Inc, University of Edinburgh, University of Southampton, National Taiwan University and Curtin University.
Associate Professor Celestial T. Yap, a clinician-scientist from the N2CR and Department of Physiology, NUS Medicine, who is a co-author of the study, said, “Triple-negative breast cancer remains particularly difficult to treat because standard options such as surgery, chemotherapy, and immunotherapy do not work equally well for all patients, and resistance and recurrence are common. What makes this finding exciting is that DP103 may represent a new biological vulnerability in the disease, linking tumour growth, stemness, and treatment resistance. This discovery offers new insights that could support more precise patient selection and open the door to better targeted strategies for durable disease control and improved clinical outcomes.”
As abnormal Wnt signalling is a driving factor behind several other cancers, the impact of the research could extend beyond breast cancer and open new avenues for treating multiple aggressive cancers. The research team’s next steps include validating DP103 as a predictive biomarker in larger patient cohorts while further developing DP103-targeted therapies for clinical testing. They will also investigate combination treatments with existing therapies to further improve treatment outcomes.
[1] https://www.nature.com/articles/nrclinonc.2016.66 ; https://jamanetwork.com/journals/jama/article-abstract/2721183
Cell Death and Disease
DP103 as a critical modulator of Wnt signaling and cancer stemness: implications for precision treatment in triple negative breast cancer
1-Aug-2026