Chemotherapy Triggers Dormant Cancer Cells: Senolytic Drugs Show Promise in Preventing Relapse

Recent research has shed light on the behavior of dormant cancer cells, particularly how chemotherapy can inadvertently awaken these cells, leading to potential relapses in patients. This study, conducted by the Shanghai Institute of Nutrition and Health, reveals significant insights into the mechanisms behind tumor recurrence following initial treatments.

Breast cancer is known for its tendency to relapse in distant organs, even after the primary tumors have been effectively treated. In many cases, dormant disseminated tumor cells (DTCs) remain in the body, evading detection and treatment through conventional chemotherapy. Until now, the activation of these dormant cells and the role of chemotherapy in this awakening were not thoroughly understood.

The researchers developed an innovative system, named DormTracer, which allows for the tracking of DTC dormancy. This system employs a doxycycline-inducible genetic marker that helps to monitor the history of DTC dormancy. Crucially, it distinguishes between dormant and active cells, providing valuable data on how chemotherapy impacts these cells.

Through their experiments, the scientists observed that chemotherapy indeed prompted the awakening of dormant DTCs, ultimately leading to lung metastasis. The findings suggest that this process is driven by factors such as senescence in fibroblasts and the formation of neutrophil extracellular traps (NETs), contributing to the transition from dormancy to active proliferation.

In response to these findings, the researchers proposed a dual treatment approach combining chemotherapy with senolytic drugs, specifically Dasatinib and Quercetin (DQ). These senolytic agents have been shown to target and induce apoptosis in senescent cells, effectively reducing the likelihood of tumor relapse. Clinical trials demonstrated that administering DQ alongside chemotherapy not only controlled primary tumors but also prevented lung metastasis.

The introduction of DormTracer is a significant advancement in cancer research, facilitating further studies into the regulation of cellular dormancy and potential interventions. The implications of this research are profound, as they offer a new strategy to enhance the effectiveness of existing cancer therapies by addressing the side effects associated with chemotherapy-induced relapses.

This study opens the door for future clinical trials aimed at refining treatment protocols and improving outcomes for patients battling cancer. By understanding the dynamics of dormant DTCs and their activation, healthcare professionals may develop more effective strategies to combat cancer recurrence.