Menyailo Maxim E, Bokova Ustinia A, Ivanyuk Elena E, Khozyainova Anna A, Denisov Evgeny V
Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str. 5, Tomsk, 634009, Russia.
Laboratory of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str. 5, Tomsk, 634009, Russia.
Mol Diagn Ther. 2021 Sep;25(5):549-562. doi: 10.1007/s40291-021-00543-5. Epub 2021 Jul 21.
Metastasis is the main cause of cancer death. Metastatic foci are derived from tumor cells that detach from the primary tumor and then enter the circulation. Circulating tumor cells (CTCs) are generally associated with a high probability of distant metastasis and a negative prognosis. Most CTCs die in the bloodstream, and only a few cells form metastases. Such metastatic CTCs have a stem-like and hybrid epithelial-mesenchymal phenotype, can avoid immune surveillance, and show increased therapy resistance. Targeting metastatic CTCs and their progenitors in primary tumors and their descendants, particularly disseminated tumor cells, represents an attractive strategy for metastasis prevention. However, current therapeutic strategies mainly target the primary tumor and only indirectly affect metastasis-initiating cells. Here, we consider potential methods for preventing metastasis based on targeting molecular and cellular features of metastatic CTCs, including CTC clusters. Also, we emphasize current knowledge gaps in CTC biology that should be addressed to develop highly effective therapeutics and strategies for metastasis suppression.
转移是癌症死亡的主要原因。转移灶源自从原发性肿瘤脱离并进入循环系统的肿瘤细胞。循环肿瘤细胞（CTC）通常与远处转移的高概率和不良预后相关。大多数CTC在血流中死亡，只有少数细胞形成转移灶。这种转移性CTC具有干细胞样和上皮-间质混合表型，能够逃避免疫监视，并表现出更高的治疗抗性。针对原发性肿瘤中的转移性CTC及其祖细胞以及它们的后代，特别是播散性肿瘤细胞，是一种有吸引力的预防转移策略。然而，目前的治疗策略主要针对原发性肿瘤，仅间接影响转移起始细胞。在这里，我们考虑基于靶向转移性CTC的分子和细胞特征（包括CTC簇）来预防转移的潜在方法。此外，我们强调在CTC生物学方面目前存在的知识空白，要开发高效的治疗方法和转移抑制策略就必须解决这些空白。
