Diagnosis and therapeutic targeting of quiescent cancer cells: road to conquer cancer recurrence

Quiescent cancer cells (QCCs) are considered an origin of cancer recurrence and present an ongoing challenge in cancer treatment. Following anti-cancer therapy, non-proliferating, therapy-resistant QCCs have been detected as subsets of residual cancer cells within patients. Clinicians and researchers widely believe that these minimal residual QCCs can eventually regain proliferative activity, acting as "seeds" for cancer recurrence. Despite the significance of QCCs, tracing and analyzing these microscopic residual cells in vivo models and patients remains extremely challenging, limiting our understanding. Consequently, reliable biomarkers for QCCs and the mechanisms underlying their 'reversible' reactivation are still poorly understood. This knowledge gap has hindered the development of diagnostics and targeted therapies for QCCs. The absence of diagnostic tools for QCCs also complicates predicting cancer relapse and determining the optimal duration of anti-cancer treatment. Moreover, without strategies to eradicate QCCs, preventing cancer recurrence remains elusive. This review aims to provide an overview of the current understanding of QCCs and related diagnostic efforts in both basic and clinical research. Additionally, potential strategies for the targeted elimination of QCCs are explored. Focused research and clinical attention to diagnosing and eradicating residual QCCs are essential for preventing cancer recurrence and ultimately conquering this deadly disease. [BMB Reports 2025; 58(7): 277-287].