Cancer cell dormancy: An update to 2025

Abstract

About 70 years ago, scientists first observed groups of cancer cells in a ``temporary mitotic ar-rest,'' a dormant state that complicates treatment and increases the risk of recurrence. Recent updates have provided novel insights into the mechanisms driving cancer cell dormancy, especially in relation to how dormant cells evolve and develop resistance to treatments over time. This phe-nomenon is particularly concerning in breast cancer, where dormant cells can 'wake up' after ex-tended periods, contributing to cancer relapse. Dormancy, akin to hibernation in animals, occurs when cancer cells enter a resting phase (G0/G1 phase) in response to stressors like nutrient depri-vation or hypoxia. Key signaling pathways have been identified that regulate the balance between proliferation and dormancy, with some pathways playing critical roles in maintaining dormancy for years. Notably, cancer dormancy has been linked to enhanced stemness and increased resistance to therapies, making drug resistance a significant challenge. Despite promising advancements, ex-isting strategies to target dormant cancer cells have not yet achieved complete eradication, leaving surviving cells that can trigger relapse. A particularly important future direction is the development of combination therapies, which hold potential for preventing recurrence and improving patient outcomes by targeting multiple mechanisms that govern dormancy and reactivation.