Puglisi Caterina, Giuffrida Raffaella, Borzì Giuseppina, Di Mattia Paolo, Costa Anna, Colarossi Cristina, Deiana Enrica, Picardo Maria Carolina, Colarossi Lorenzo, Mare Marzia, Marino Lorenza, Di Grazia Alfio, Forte Stefano
IOM Ricerca Srl, Viagrande, I-95029 Catania, Italy.
REM Radioterapia, Viagrande, I-95029 Catania, Italy.
Cancers (Basel). 2020 Dec 7;12(12):3672. doi: 10.3390/cancers12123672.
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.
新辅助放疗常用于局部晚期直肠癌（LARC）的治疗管理。放疗既能减少局部复发，又能通过缩小肿瘤肿块大小提高手术成功率。然而，一些患者对治疗反应不佳，导致出现原发性耐药或在看似根治性手术后复发。在这项研究中，我们报告了基于患者来源的癌症干细胞（CSC）的体外和体内模型；这些模型能够预测LARC患者对放疗的个体反应。从结直肠癌活检组织中分离出的CSC，按照用于LARC患者的相同临床方案进行体外照射。通过CSC异种移植生成的动物模型也获得了，并采用相同的放疗方案进行治疗。结果表明，从直肠癌穿刺活检中分离出的CSC对治疗具有内在的敏感性等级，这在动物模型中也得以保持。值得注意的是，特定CSC的体外和体内敏感性值与患者对放疗的反应相对应。这一证据表明，体外放疗反应预测性检测可为LARC患者的管理提供临床决策支持，从而避免对耐药患者产生放射毒性并降低治疗成本。
