Predicting therapy response by analysis of metastasis founder cells: emerging perspectives for personalized tumor therapy

Introduction: Circulating tumor and disseminated cancer cells can be detected after surgical removal of the primary tumor in non-metastatic patients. Despite being considered the prime targets of adjuvant therapy, they have not been implemented into clinical decision making yet. Areas covered: Here we review the recent progress in understanding the biology of circulating tumor cells and disseminated cancer cells as well as the technical challenges associated with quantification, isolation, and preclinical model development. We highlight the first examples of clinical studies in which metastasis founder cells have been used as surrogate markers in adjuvant cancer patients and address the current hurdles in implementing these in routine clinical application. Finally, we provide a perspective on how the combination of technologies to detect and isolate metastasis founders, single-cell multi-omics, development of preclinical models, and their drug responses in specific nich es could improve personalized adjuvant treatment strategies. Expert opinion: The specific target cells of adjuvant cancer treatment are metastasis founder cells that remain in the body of the patients after surgical removal of the primary tumor. We, therefore, believe that the success of adjuvant therapies will be improved by implementing circulating and disseminated cancer cells in future clinical decision making.