D'Andrea V, Guarino S, Di Matteo F M, Maugeri Saccà M, De Maria R
G Chir. 2014 Nov-Dec;35(11-12):257-9.
The Cancer Stem Cells (CSC) hypothesis is based on three fundamental ideas: 1) the similarities in the mechanisms that regulate self-renewal of normal stem cells and cancer cells; 2) the possibility that tumour cells might arise from normal stem cells; 3) the notion that tumours might contain 'cancer stem cells' - rare cells with indefinite proliferative potential that drive the formation and growth of tumours. The roles for cancer stem cells have been demonstrated for some cancers, such as cancers of the hematopoietic system, breast, brain, prostate, pancreas and liver. The attractive idea about cancer stem cell hypothesis is that it could partially explain the concept of minimal residual disease. After surgical macroscopically zero residual (R0) resections, even the persistence of one single cell nestling in one of the so called "CSCs niches" could give rise to distant relapse. Furthermore the metastatic cells can remain in a "dormant status" and give rise to disease after long period of apparent disease free. These cells in many cases have acquired resistance traits to chemo and radiotherapy making adjuvant treatment vain. Clarifying the role of the cancer stem cells and their implications in the oncogenesis will play an important role in the management of cancer patient by identifying new prospective for drugs and specific markers to prevent and monitoring relapse and metastasis. The identification of the niche where the CSCs reside in a dormant status might represent a valid instrument to follow-up patients also after having obtained a R0 surgical resection. What we believe is that if new diagnostic instruments were developed specifically to identify the localization and status of activity of the CSCs during tumor dormancy, this would lead to impressive improvement in the early detection and management of relapse and metastasis.
癌症干细胞(CSC)假说基于三个基本观点:1)调节正常干细胞和癌细胞自我更新的机制具有相似性;2)肿瘤细胞可能起源于正常干细胞;3)肿瘤可能包含“癌症干细胞”——具有无限增殖潜能的罕见细胞,驱动肿瘤的形成和生长。癌症干细胞的作用已在某些癌症中得到证实,如造血系统、乳腺、脑、前列腺、胰腺和肝脏的癌症。癌症干细胞假说的诱人之处在于,它可以部分解释微小残留病的概念。在进行手术宏观上零残留(R0)切除后,即使在所谓的“癌症干细胞龛”之一中残留一个单细胞,也可能导致远处复发。此外,转移细胞可以保持“休眠状态”,在长期无明显疾病后引发疾病。这些细胞在许多情况下已经获得了对化疗和放疗的耐药特性,使得辅助治疗徒劳无功。阐明癌症干细胞的作用及其在肿瘤发生中的意义,将通过确定预防和监测复发及转移的新药和特定标志物的新前景,在癌症患者的管理中发挥重要作用。识别癌症干细胞处于休眠状态的龛位,可能是在获得R0手术切除后对患者进行随访的有效手段。我们认为,如果专门开发新的诊断工具来识别肿瘤休眠期间癌症干细胞的定位和活性状态,这将在复发和转移的早期检测和管理方面带来显著改善。