Inspired by Nature: Enhancing p53 to Prevent Cancer Before It Starts
Cancer incidence is rising globally, with one in four individuals expected to develop the disease during their lifetime. This sobering statistic has driven decades of research into the mechanisms that drive cancer, with the aim of developing better therapies and, ultimately, preventing what some describe as an impending “cancer tsunami.”
A recent study by researchers from NTU’s School of Biological Sciences (SBS) presents a promising strategy to proactively delay or prevent cancer formation – a potential breakthrough that could help stem this looming crisis.
Professor Kanaga Sabapathy, Chair of SBS, and Mr. Christian Krueger have adopted a preventive approach focused on modulating wild-type p53 levels, aiming to delay or even prevent tumour formation. Their research was published in Nature’s Cell Death & Differentiation in June 2025.
Nature’s Secret Weapon Against Cancer: Lessons Inspired by Elephants
TP53 is the most frequently mutated gene in human cancers. Individuals born with a faulty copy, such as those with Li-Fraumeni syndrome (LFS), face a significantly increased lifetime risk of developing multiple types of cancer, often from a young age. Unfortunately, there are currently no preventive treatment options available for these high-risk individuals.
This is where our SBS researchers drew inspiration from nature. Unlike humans, some animals, notably elephants, have evolved to carry multiple copies of the TP53 gene. This distinctive trait is believed to underlie their relative resistance to cancer. The study suggests that controlled overexpression of p53 may represent nature’s own strategy for preventing tumour development.
Adding a Third Copy of Trp53 Delays Tumours in Mice
Researchers used mice with an additional (third) copy of the Trp53 gene, either from birth or activated in adulthood, to test its impact on tumour development.
Prof. Sabapathy and Mr. Krueger tested this idea directly by modulating wild‑type p53 levels to see whether they could mitigate cancer risk. They used genetically engineered mice to carry a third copy of Trp53, introducing it either constitutively from birth or in an inducible manner during adulthood. In both settings, the mice developed tumours much later and lived longer without observable side effects.
These findings provide clear genetic evidence that a controlled, modest increase in p53 activity can act as a prophylactic defence against cancer, pointing to a promising new direction for LFS carriers and other cancer‑prone populations with reduced p53 function.
Redefining Cancer Prevention: A New Path Forward
This breakthrough study by our SBS researchers marks a significant advance in efforts to reduce cancer incidence in the years ahead. We often look to nature for inspiration, and this time nature has provided valuable insights that helped our researchers explore new strategies with potential benefits for both high-risk groups and the broader population at risk of cancer.
Kudos to Prof. Sabapathy and Mr. Krueger for their outstanding discovery and important contribution to cancer prevention research!
Read the full paper here.