Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers

Frontiers in Immunology

Immunology

Olga A. Rakitina¹  Victor V. Pleshkan²  Irina V. Alekseenko³  Julian M. Rozenberg⁴  Tharaa Mohammad⁴  Anton A. Buzdin⁵  Dmitry A. Didych⁶ 

[1] Gene Immunooncotherapy Group, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia;Gene Immunooncotherapy Group, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia;Gene oncotherapy sector, Institute of Molecular Genetics of National Research Centre (Kurchatov Institute), Moscow, Russia;Gene Immunooncotherapy Group, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia;Gene oncotherapy sector, Institute of Molecular Genetics of National Research Centre (Kurchatov Institute), Moscow, Russia;Laboratory of Epigenetics, Institute of Oncogynecology and Mammology, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov, Ministry of Healthcare of the Russian Federation, Moscow, Russia;Laboratory of Translational Bioinformatics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia;Laboratory of Translational Bioinformatics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia;PathoBiology Group, European Organization for Research and Treatment of Cancer (EORTC), Brussels, Belgium;Group for Genomic Analysis of Cell Signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia;Laboratory for Clinical Genomic Bioinformatics, Sechenov First Moscow State Medical University, Moscow, Russia;Laboratory of human genes structure and functions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia;

关键词: cancer;    metastasis;    circulating cancer cell;    tumor microenvironment;    heterotypic cell interactions;   

DOI  :  10.3389/fimmu.2023.1099921

 received in 2022-11-16, accepted in 2023-02-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.

【 授权许可】

Unknown   
Copyright © 2023 Rozenberg, Buzdin, Mohammad, Rakitina, Didych, Pleshkan and Alekseenko