TY - JOUR
T1 - Insights into new mechanisms and models of cancer stem cell multidrug resistance
AU - Garcia-Mayea, Y.
AU - Mir, C.
AU - Masson, F.
AU - Paciucci, R.
AU - LLeonart, M. E.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - © 2019 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.
AB - © 2019 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.
KW - Cancer
KW - Cancer stem cells
KW - Chemoresistance
KW - Multidrug
KW - Therapy
U2 - 10.1016/j.semcancer.2019.07.022
DO - 10.1016/j.semcancer.2019.07.022
M3 - Review article
C2 - 31369817
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
SN - 1044-579X
ER -