Vinnitsky Vladimir
Department of Experimental Cancer Therapeutics; R.E. Kavetsky Institute for Experimental Pathology, Oncology, and Radiobiology; Kiev, Ukraine; Sequent Development (CRO), LLC; Madison, VA USA.
Intrinsically Disord Proteins. 2014 Jul 18;2(1):e29997. doi: 10.4161/idp.29997. eCollection 2014.
To date there is no explanation why the development of almost all types of solid tumors occurs sharing a similar scenario: (1) creation of a cancer stem cell (CSC), (2) CSC multiplication and formation of a multicellular tumor spheroid (TS), (3) vascularization of the TS and its transformation into a vascularized primary tumor, (4) metastatic spreading of CSCs, (5) formation of a metastatic TSs and its transformation into metastatic tumors, and (6) potentially endless repetition of this cycle of events. The above gaps in our knowledge are related to the biology of cancer and specifically to tumorigenesis, which covers the process from the creation of a CSC to the formation of a malignant tumor and the development of metastases. My Oncogerminative Theory of Tumorigenesis considers tumor formation as a dynamic self-organizing process that mimics a self-organizing process of early embryo development. In the initial step in that process, gene mutations combined with epigenetic dysregulation cause somatic cells to be reprogrammed into CSCs, which are immortal pseudo-germline cells. Mimicking the behavior of fertilized germline cells, the CSC achieves immortality by passing through the stages of its life-cycle and developing into a pseudo-blastula-stage embryo, which manifests in the body as a malignant tumor. In this view, the development of a malignant tumor from a CSC is a phenomenon of developmental biology, which we named a desperate asexual self-cloning event. The theory explains seven core characteristics of malignant tumors: (1) CSC immortality, (2) multistep development of a malignant tumor from a single CSC, (3) heterogeneity of malignant tumor cell populations, (4) metastatic spread of CSCs, (5) invasive growth, (6) malignant progression, and (7) selective immune tolerance toward cancer cells. The Oncogerminative Theory of Tumorigenesis suggests new avenues for discovery of revolutionary therapies to treat, prevent, and eradicate cancer.
迄今为止,对于几乎所有类型实体瘤的发生发展为何都呈现出相似的情形,尚无解释:(1) 癌症干细胞(CSC)的产生;(2) CSC 的增殖以及多细胞肿瘤球体(TS)的形成;(3) TS 的血管化及其转变为血管化的原发性肿瘤;(4) CSC 的转移扩散;(5) 转移性 TS 的形成及其转变为转移性肿瘤;以及(6) 这一系列事件循环可能无休止地重复。我们知识上的上述空白与癌症生物学相关,尤其与肿瘤发生相关,肿瘤发生涵盖了从 CSC 的产生到恶性肿瘤的形成以及转移发展的过程。我的肿瘤发生的胚源理论认为肿瘤形成是一个动态的自组织过程,类似于早期胚胎发育的自组织过程。在该过程的初始步骤中,基因突变与表观遗传失调导致体细胞被重新编程为 CSC,CSC 是永生的假生殖系细胞。CSC 通过经历其生命周期的各个阶段并发育成假囊胚期胚胎来实现永生,在体内表现为恶性肿瘤。从这个角度来看,从 CSC 发展出恶性肿瘤是发育生物学的一种现象,我们将其命名为绝望的无性自我克隆事件。该理论解释了恶性肿瘤的七个核心特征:(1) CSC 的永生性;(2) 从单个 CSC 多步骤发展为恶性肿瘤;(3) 恶性肿瘤细胞群体的异质性;(4) CSC 的转移扩散;(5) 侵袭性生长;(6) 恶性进展;以及(7) 对癌细胞的选择性免疫耐受。肿瘤发生的胚源理论为发现治疗、预防和根除癌症的革命性疗法指明了新途径。