Many cancer cells consume a lot of glucose to grow.
An experimental molecule exploits this dependence in an unexpected way: it speeds up their consumption, then disrupts another energy pathway. Tested on cells and mice, it slowed tumor growth without causing visible weight loss during the experiment.
The molecule, called XJ-4-85, targets PFKL, an enzyme that controls a key step of glycolysis. Glycolysis is the series of reactions that converts glucose into energy and materials usable by the cell. Many tumors rely heavily on this pathway, even when oxygen is not lacking.
Usually, an anticancer strategy instead seeks to slow down this fuel. Here, the researchers did the opposite.
XJ-4-85 binds persistently to a specific site on PFKL and keeps the enzyme in its active form. This activation pushes more glucose into glycolysis. Measurements in several cell types showed a rapid increase in the products of this pathway, as well as an increase in its overall activity.
But the molecule does not simply press the accelerator. When it binds to PFKL, it also releases a second part that blocks CPT2, a protein involved in the use of fats by mitochondria. In other words, it stimulates one energy source while hindering another backup solution.
This dual effect could explain why tumor cells were more sensitive than several non-cancerous cell lines studied in the laboratory.
To verify its action in a living organism, the team implanted melanoma cells into mice. When the tumors reached about 100 mm³, the animals received the molecule or various comparison products every day. After two weeks, tumor growth was clearly reduced with XJ-4-85.
Genetic experiments then strengthened the interpretation. When PFKL was removed from tumor cells, efficacy decreased strongly. Suppression of CPT2 also reduced the response. These results indicate that both targets contribute to the observed effect, rather than simple general toxicity.
Now the next step is to turn this chemical principle into a therapeutic candidate. The researchers will need to measure its distribution in the body, its safety over a longer period, and its efficacy in other cancer models.