TY - JOUR
T1 - Cancer drug-tolerant Persister cells: from biological questions to clinical opportunities
AU - Russo, Mariangela
AU - Chen, Mengnuo
AU - Mariella, Elisa
AU - Peng, Haoning
AU - Rehman, Sumaiyah K.
AU - Sancho, Elena
AU - Sogari, Alberto
AU - Toh, Tzen S.
AU - Balaban, Nathalie Q.
AU - Batlle, Eduard
AU - Bernards, Rene
AU - Garnett, Mathew J
AU - Hangauer, Matthew
AU - Leucci, Eleonora
AU - Marine, Jean-Christophe
AU - O’Brien, Catherine A.
AU - Oren, Yaara
AU - Patton, E Elizabeth
AU - Robert, Caroline
AU - Rosenberg, Susan M.
AU - Shen, Shensi
AU - Bardelli, Alberto
PY - 2024/9/2
Y1 - 2024/9/2
N2 - The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant ‘persister’ (DTP) cells, play a prominent role in drug resistance. While long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the last two decades, yet several aspects of their biology remain enigmatic. Here we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit remarkable plasticity, being capable of transitioning between different cellular states, resulting in distinct DTP phenotypes within a single tumor. However, defining the biological features of DTPs has been challenging, partly due to the complex interplay between clonal dynamics and tissue-specific factors influencing their phenotype. Moreover, the interactions between DTPs and the tumor microenvironment, including their potential to evade immune surveillance, remain to be discovered. Lastly, the mechanisms underlying DTP-derived drug resistance and their correlation with clinical outcomes remain poorly understood. This Roadmap aims to provide a comprehensive overview of the field of DTPs, encompassing past achievements and current endeavors in elucidating their biology. We also discuss the prospect of future advancements in technologies in helping to unveil the features of DTPs and propose novel therapeutic strategies that could lead to their eradication.
AB - The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant ‘persister’ (DTP) cells, play a prominent role in drug resistance. While long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the last two decades, yet several aspects of their biology remain enigmatic. Here we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit remarkable plasticity, being capable of transitioning between different cellular states, resulting in distinct DTP phenotypes within a single tumor. However, defining the biological features of DTPs has been challenging, partly due to the complex interplay between clonal dynamics and tissue-specific factors influencing their phenotype. Moreover, the interactions between DTPs and the tumor microenvironment, including their potential to evade immune surveillance, remain to be discovered. Lastly, the mechanisms underlying DTP-derived drug resistance and their correlation with clinical outcomes remain poorly understood. This Roadmap aims to provide a comprehensive overview of the field of DTPs, encompassing past achievements and current endeavors in elucidating their biology. We also discuss the prospect of future advancements in technologies in helping to unveil the features of DTPs and propose novel therapeutic strategies that could lead to their eradication.
U2 - 10.1038/s41568-024-00737-z
DO - 10.1038/s41568-024-00737-z
M3 - Review article
SN - 1474-175X
JO - Nature Reviews Cancer
JF - Nature Reviews Cancer
ER -