Chemotherapy and other treatments destroy many cancer cells, but not all of them die. Some stop dividing and enter a state of "senescence." This may seem harmless at first, but these senescent cancer cells still release substances—senescence-associated secretory phenotype (SASP)—that can cause inflammation and damage the body. This increases the risk of tumor metastasis and worsens prognosis.
Using the CRISPR-Cas9 gene-editing technique, the researchers uncovered an unexpected vulnerability in these senescent cancer cells: the protein SLC25A23, which transports calcium. The antibiotic salinomycin can disrupt the function of this protein, killing senescent cancer cells. The researchers had previously identified another way to kill senescent cancer cells, and now found that combining the two drugs significantly enhances their effectiveness. On top of killing the cancer cells themselves, the drug combination activates the immune system to attack the cancer cells as well. “The combination of these two drugs triggers a unique triple cell-death mechanism and also activates the immune system,” says Rene Bernards, group leader at the Netherlands Cancer Institute and lead researcher of this study.
The researchers observed that this drug combination significantly inhibited tumor growth in mice, and these results were effective even in lower doses, reducing the risk of side effects. Additionally, the drug combination increased the activity of immune cells such as natural killer cells and CD8+ T-cells, which play a key role in attacking tumors. Bernards: “This means that the treatment can directly kill cancer cells as well as supporting the body’s own immune system.”
Many cancer patients suffer from the harmful effects of senescent cells, as these cells can also form in normal tissues as a side effect of cancer therapy. This new approach could potentially target these cells while simultaneously activating the immune system. This would help control tumors more effectively as well as potentially reduce the side effects of chemotherapy.
Although the results are promising, this study is still in its early stages. The drugs need further testing in clinical trials before they can be available to patients. If these trials are successful, this therapy could offer improved treatment options for cancer patients in the future. This research highlights the potential in repurposing existing drugs for cancer treatment. Salinomycin is currently used in poultry feed to suppress bacterial infections. In the future, it may also play a role in cancer therapy.