Radiosensitivity of Cancer Stem Cells Has Potential Predictive Value for Individual Responses to Radiotherapy in Locally Advanced Rectal Cancer

SIMPLE SUMMARY: Radiotherapy is often used as a neo-adjuvant treatment in locally advanced rectal cancer. While treatment generally induces an improvement in the outcome, some patients show resistance to treatment for reasons that still have to be elucidated. In this work, we report an in vitro and in vivo model based on patient-derived cancer stem cells. This model is able to predict individual responses to radiotherapy. The results indicate that cells found to be radiation-sensitive in vitro generated radiation-sensitive tumor xenografts upon subcutaneous implantation. Analogously, cancer stem cells (CSCs) that did not respond to in vitro radiation treatment generated radiation-resistant tumor xenografts. Moreover, radioresistant CSCs were generally isolated via biopsies of patients with poor responses to neo-adjuvant radiotherapy. This suggests that a cell-based in vitro test may itself be sufficient to predict outcomes in donor patients. ABSTRACT: Neo-adjuvant radiotherapy is frequently employed in the therapeutic management of locally advanced rectal cancer (LARC). Radiotherapy can both reduce local recurrence and improve the success of surgical procedures by reducing tumor mass size. However, some patients show a poor response to treatment, which results in primary resistance or relapse after apparent curative surgery. In this work, we report in vitro and in vivo models based on patient-derived cancer stem cells (CSCs); these models are able to predict individual responses to radiotherapy in LARC. CSCs isolated from colorectal cancer biopsies were subjected to in vitro irradiation with the same clinical protocol used for LARC patients. Animal models, generated by CSC xenotransplantation, were also obtained and treated with the same radiotherapy protocol. The results indicate that CSCs isolated from rectal cancer needle biopsies possess an intrinsic grade of sensitivity to treatment, which is also maintained in the animal model. Notably, the specific CSCs’ in vitro and in vivo sensitivity values correspond to patients’ responses to radiotherapy. This evidence suggests that an in vitro radiotherapy response predictivity assay could support clinical decisions for the management of LARC patients, thus avoiding radiation toxicity to resistant patients and reducing the treatment costs.