Abstract
QCCs have long gained significant interest as potential "seeds" for recurrent cancers. Clinical evidence suggests that a subset of cancer cells exits the cell cycle and enters a quiescent state following anti-cancer treatment. These microscopic-residual QCCs are extremely challenging to trace and detect within patients. Additionally, QCCs resist conventional anti-cancer therapies due to the lack of cell activity. Notably, upon the unknown environmental cues in unknown time points, sometimes decades later, QCCs can reactivate, triggering cancer relapse at primary or secondary sites. Currently, no targeted therapies or diagnostic tools exist for QCCs, and their molecular regulatory mechanisms remain largely unknown. The major challenge in understanding QCCs lies in the limited availability of human-relevant pre-clinical models that trace and collect QCCs in vivo. This review provides an overview of existing QCC tracing systems and analyzes their limitations. It also cautiously proposes potential improvements for tracing QCCs in vivo based on recent advancements in QCC studies and lineage-tracing techniques. Developing human-relevant and easily accessible in vivo tracing systems will be a crucial step in advancing QCC diagnostics and therapeutic strategies.