A cell cycle centric view of tumour dormancy

Tumour dormancy and recurrent metastatic cancer remain the greatest clinical challenge for cancer patients. Dormant tumour cells can evade treatment and detection, while retaining proliferative potential, often for years, before relapsing to tumour outgrowth. Cellular quiescence is one mechanism that promotes and maintains tumour dormancy due to its central role in reducing proliferation, elevating cyto-protective mechanisms, and retaining proliferative potential. Quiescence/proliferation decisions are dictated by intrinsic and extrinsic signals, which regulate the activity of cyclin-dependent kinases (CDKs) to modulate cell cycle gene expression. By clarifying the pathways regulating CDK activity and the signals which activate them, we can better understand how cancer cells enter, maintain, and escape from quiescence throughout the progression of dormancy and metastatic disease. Here we review how CDK activity is regulated to modulate cellular quiescence in the context of tumour dormancy and highlight the therapeutic challenges and opportunities it presents.

Automated summary

Tumour dormancy and recurrent metastatic cancer pose significant challenges in cancer treatment. Cellular quiescence plays a central role in promoting and maintaining tumour dormancy by reducing proliferation and enhancing cyto-protective mechanisms. Understanding the regulation of cyclin-dependent kinases (CDKs) and the signals that activate them can shed light on the mechanisms of cancer cell quiescence, thus providing opportunities for therapeutic intervention. This review discusses the regulation of CDK activity in cellular quiescence during tumour dormancy and highlights the therapeutic challenges and opportunities associated with it.