In a breakthrough that could reshape cancer treatment, scientists at Chiba University in Japan have discovered that cholesterol helps certain cancer cells survive high temperatures, potentially explaining why some tumors resist heat-based therapies. The study, published in Scientific Reports in 2025, sheds light on a major obstacle in hyperthermia therapy, one that might now be overcome.

Hyperthermia, a technique that heats tumors to about 50 °C, is known to kill cancer cells while sparing healthy tissue. It also helps activate the immune system, making it a promising companion to immunotherapy. But until now, doctors have puzzled over why some tumors stubbornly withstand the heat. The answer, it turns out, may lie in cholesterol. The researchers found that heat-resistant cancer cells contain far more cholesterol in their membranes than heat-sensitive ones. This extra cholesterol acts like a shield, preventing the membranes from becoming too fluid under heat stress and protecting the cells from the physical damage that would otherwise cause them to die.

To test this theory, the team used cholesterol-depleting drugs in lab-grown cells and in mice with implanted tumors. The results were striking: when cholesterol was reduced, cancer cells became far more vulnerable to heat. In mouse models, the combination of cholesterol depletion and targeted heat treatment led to the dramatic shrinkage—and often total disappearance—of tumors. These outcomes were far better than those achieved by heat treatment alone.

The implications could be wide-reaching. For one, measuring cholesterol levels in tumors might help predict which patients would benefit most from hyperthermia. More importantly, the combination of cholesterol-lowering drugs and heat therapy could make hyperthermia a much more reliable and powerful tool in the cancer arsenal. Since this approach triggers a form of cell death called necrosis, which tends to stimulate immune responses, it may also help improve the effectiveness of cancer immunotherapies—currently successful in only a small percentage of patients.

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