癌症干细胞
癌症
转移
癌症研究
肿瘤微环境
干细胞
癌细胞
生物
肿瘤进展
免疫学
遗传学
作者
Yoelsis García-Mayea,Cristina Mir,Frédéric Masson,Rosanna Paciucci,Matilde E. Lleonart
标识
DOI:10.1016/j.semcancer.2019.07.022
摘要
The acquisition of genetic alterations, clonal evolution, and the tumor microenvironment promote cancer progression, metastasis and therapy resistance. These events correspond to the establishment of the great phenotypic heterogeneity and plasticity of cancer cells that contribute to tumor progression and resistant disease. Targeting resistant cancers is a major challenge in oncology; however, the underlying processes are not yet fully understood. Even though current treatments can reduce tumor size and increase life expectancy, relapse and multidrug resistance (MDR) ultimately remain the second cause of death in developed countries. Recent evidence points toward stem-like phenotypes in cancer cells, promoted by cancer stem cells (CSCs), as the main culprit of cancer relapse, resistance (radiotherapy, hormone therapy, and/or chemotherapy) and metastasis. Many mechanisms have been proposed for CSC resistance, such as drug efflux through ABC transporters, overactivation of the DNA damage response (DDR), apoptosis evasion, prosurvival pathways activation, cell cycle promotion and/or cell metabolic alterations. Nonetheless, targeted therapy toward these specific CSC mechanisms is only partially effective to prevent or abolish resistance, suggesting underlying additional causes for CSC resilience. This article aims to provide an integrated picture of the MDR mechanisms that operate in CSCs’ behavior and to propose a novel model of tumor evolution during chemotherapy. Targeting the pathways mentioned here might hold promise and reveal new strategies for future clinical therapeutic approaches.
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