Despite advances in cancer treatment, two of the main challenges that persist are cancer cells that resist therapy, and treatments that harm healthy tissue. Biomedical scientist, medical doctor and Professor at the University of Pretoria’s (UP) Department of Physiology, Joji Mercier, addressed this during her inaugural lecture titled: ‘Molecular mechanisms of novel candidate molecules to overcome cancer treatment resistance,’ delivered on 13 August 2025 at the University’s Hatfield Campus.

She explained that while conventional treatments such as surgery, radiation and chemotherapy remain central to care, they’re constrained both by the toxicity they cause to healthy tissues and by the ability of cancer cells to adapt and survive. This combination of “intrinsic and acquired treatment resistance” makes remission more difficult to achieve, while dose-limiting side effects restrict how much therapy can safely be given.

Prof Mercier’s research focuses on identifying and testing new molecules that can attack cancer cells in ways that traditional therapies cannot. The goal is to kill cancer cells selectively, sparing healthy cells and widening what oncologists call the “therapeutic window.” This is the balance between giving enough of a treatment to target cancer cells effectively, while keeping the dose low enough to avoid serious harm to healthy tissues.

One strategy is to use radiosensitizers, compounds that make tumour cells more vulnerable to radiation. These compounds, Prof Mercier explained, “aim to overcome resistance and widen the therapeutic window by selectively increasing tumour cell sensitivity to radiation”.

This means patients could potentially receive lower doses of radiation with the same or better effect, reducing the harm to normal tissue.

Some of these molecules copy natural hormones, some are built on special chemical structures and others are completely new designs. All these molecules can make cancer cells more vulnerable to treatment while sparing healthy cells.

How new molecules make cancer treatment safer and more effective

Prof Mercier explained that her research began with testing compounds called oestradiol analogues, which are computer-designed modified versions of the natural hormone. These molecules were able to trigger cancer cell death through several processes at once, while still working against cells that had already become resistant to multiple anticancer drugs.

Importantly, they also stopped the growth of new blood vessels that feed tumours. When used in small doses before radiation therapy, these compounds made cancer cells more sensitive to treatment without harming healthy bone and blood stem cells.

Similar results were later achieved with a different family of compounds, tested in partnership with Oxford University. More recently, Prof Mercier’s team has been collaborating with French researchers on testing a carbazole derivative. This shows promise not only in making resistant cancer cells respond to chemotherapy but also in protecting patients from painful side effects such as nerve damage. Current experiments are also looking at how this compound, and tiny gold particles called nanoclusters, could improve the effects of radiation in advanced tumour models.

Innovation and affordability

“While scientific innovation is critical, we also need to think about affordability. In countries such as South Africa where resources are limited, treatments must also be accessible to patients,” Prof Mercier said. “The challenge is to combine affordability with improved clinical outcomes.”

She said her long-term vision is to advance the science of radiosensitization and novel chemotherapeutics, and to translate these findings into targeted treatments that can be made available to South African patients.

Looking ahead, Prof Mercier emphasised that a key priority is training the next generation of scientists and ensuring that advanced molecular techniques are sustained locally. Her research is also moving towards clinical application. By testing these compounds on tumour samples taken from patients, her team aims to identify markers that can predict which treatments will work best, helping doctors personalise cancer care.