Insights from Xiaonan Lab

Key Scientific Insights

Quiescent cancer cells (QCCs) represent a central driver of therapy resistance, tumour relapse, and metastatic progression across multiple solid tumour types, including neuroblastoma, triple-negative breast cancer, and ovarian cancer. The development of robust QCC-reporter cell models has enabled reliable discrimination between quiescent and proliferating tumour cell populations, addressing a major technical bottleneck in the field.

Using these models, we identified two genes that are selectively essential for QCC survival, highlighting cancer-specific vulnerabilities that are not required for proliferating tumour cells. One of the identified QCC-essential genes shows a strong functional link to mitochondrial regulation, revealing a previously underexplored connection between cellular dormancy and metabolic reprogramming. These findings suggest that QCCs rely on distinct metabolic adaptations to maintain long-term survival, providing a rationale for targeting mitochondrial function as an anti-relapse strategy.

Translational & Therapeutic Insights

Targeting QCC-specific survival pathways offers a promising therapeutic avenue to eliminate dormant tumour reservoirs that escape conventional cytotoxic therapies. High-throughput screening efforts have identified novel small-molecule inhibitors against QCC-essential genes, laying the foundation for precision-based therapeutic development. The selectivity of these targets for quiescent cells raises the potential for treatments with reduced toxicity toward normal proliferating tissues. Our work supports a paradigm shift from solely targeting tumour bulk to proactively eliminating dormant, relapse-initiating cell populations.

Strategic & Field-Level Insights

The ability to study QCCs across multiple tumour contexts strengthens the generalizability of our findings and supports the existence of conserved quiescence-associated survival mechanisms. These insights are particularly relevant for paediatric and young adult cancers, where long-term relapse remains a major unmet clinical challenge. By integrating molecular biology, metabolic profiling, and translational drug discovery, our research bridges fundamental cancer biology with clinically actionable outcomes.

Collectively, our findings position QCCs as a critical and druggable vulnerability in solid tumours, with the potential to significantly improve long-term patient survival.