Circulating tumour cell (CTC)-derived organoids are changing cancer research, providing scientists with a powerful tool for studying drug resistance and informing the development of new personalised therapies.
Circulating tumour cells (CTCs) are malignant cells that detach from primary or metastatic tumours and enter the bloodstream. As a central component of liquid biopsy, they provide real-time insights into tumour metastasis, the effectiveness of therapies and opportunities for personalising therapies.
The promise and challenge of CTC-derived organoids
Recently, researchers have succeeded in generating organoids from CTCs – miniature, three-dimensional tumour models that replicate key features of the original cancer. These organoids are fast becoming powerful tools for investigating metastasis and testing potential therapies. However, the field still faces major hurdles. CTCs are very rare, difficult to isolate and challenging to grow in culture – which means that success rates in constructing reliable models remain low.
A key feature of CTCs is their heterogeneity. Their surface markers and molecular traits vary from patient to patient. One of the most important biological processes linked to CTC behaviour is epithelial-mesenchymal transition (EMT). This process enables cells to break away from the primary tumour, adapt to the hostile conditions of the bloodstream and increase their metastatic potential.
Once in circulation, CTCs do not act alone. They interact with blood components such as neutrophils, platelets and macrophages, which help them survive and establish new tumour sites. Interestingly, clusters of CTCs – rather than single cells – have been shown to possess stronger metastatic potential and higher prognostic value – making them a key focus of research.
Advances in isolation and culture
Isolating and enriching CTCs is technically demanding. Traditional approaches rely on physical properties such as size and density, while others use biological markers like EpCAM and CD45. More recently, microfluidic chip technologies have massively improved the efficiency and purity of captured cells.
Once isolated, CTCs must be grown under carefully controlled conditions that replicate aspects of the tumour microenvironment. Successful culture often depends on creating hypoxic conditions, providing three-dimensional scaffolds and supplying a specific mix of growth factors. These refinements have enabled researchers to generate organoids that closely mimic patient tumours.
Applications of CTC-derived organoids
CTC-derived organoids are proving invaluable across multiple areas of oncology. In basic research, they provide unique insights into metastatic mechanisms, drug resistance, cancer stem cell properties and tumour–microenvironment interactions. In translational medicine, they enable high-throughput drug screening and the development of patient-derived xenograft models. Clinically, these organoids could help to guide treatment decisions, predicting prognosis and even enable early cancer detection.
Current limitations and future directions
Despite this promise, technical bottlenecks remain. Capture efficiency is still limited, culture success rates are not optimal and existing models do not fully replicate the complexity of the tumour microenvironment. Looking ahead, progress will depend on developing more precise capture strategies and optimising culture conditions. Combining organoid technology with multi-omics data and artificial intelligence also offers exciting possibilities for enhancing both research and clinical application.
Conclusion: bridging research and clinical practice
CTC-derived organoids are emerging as a vital bridge between laboratory research and patient care. They provide an unprecedented opportunity to study how cancer spreads and how tumours respond to treatment, while potentially providing a basis for more personalised and less invasive approaches to oncology. With continued technological innovation and the establishment of standardised protocols, these organoids are going to play an important role in the future of precision cancer medicine.