Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Ulitsa Miklukho-Maklaya, 16/10, 117997, Moscow, Russia.
Bioessays. 2018 Nov;40(11):e1800079. doi: 10.1002/bies.201800079. Epub 2018 Sep 6.
During tumor evolution, cancer cells use the tumor-stroma crosstalk to reorganize the microenvironment for maximum robustness of the tumor. The success of immune checkpoint therapy foretells a new cancer therapy paradigm: an effective cancer treatment should not aim to influence the individual components of super complex intracellular interactomes (molecular targeting), but try to disrupt the intercellular interactions between cancer and stromal cells, thus breaking the tumor as a whole. Arguments are provided in favor of a hypothesis that such interactions include formation of synapse-like structures (interfaces) where the interacting cells are located at a distance of ∼10-15 nm. Within these interfaces, molecules initiating and strengthening the interaction are organized, and allow optimum cross-signaling; a very confined intercellular space facilitates the concentration of secreted cytokines, enhancing the paracrine cross-communication. These features of tumors form a druggable cancer hallmark the tumor-stroma symbiotic crosstalk-which represents a new target for efficient cancer drug discovery.
在肿瘤进化过程中，癌细胞利用肿瘤-基质的串扰来重新组织微环境，以使肿瘤具有最大的稳健性。免疫检查点治疗的成功预示着一种新的癌症治疗范例：有效的癌症治疗不应旨在影响超级复杂细胞内相互作用组的单个成分（分子靶向），而是尝试破坏癌细胞与基质细胞之间的细胞间相互作用，从而破坏整个肿瘤。有论据支持这样一种假设，即这些相互作用包括形成类似于突触的结构（界面），其中相互作用的细胞位于距离约 10-15nm 的位置。在这些界面内，启动和增强相互作用的分子被组织起来，并允许最佳的交叉信号转导；非常受限的细胞间空间促进了分泌细胞因子的浓缩，增强了旁分泌交叉通讯。这些肿瘤特征形成了可药物治疗的癌症标志——肿瘤-基质共生串扰，这代表了有效癌症药物发现的新靶点。
