首页|Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

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Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer treatment.Since tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the tumor.Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy.We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"popula-tions.Furthermore,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells.Beyond understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CSCs)and their dual and intertwined functions based on their cell cycle state in response to treatment.More-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors.Overall,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

Cancer stem cells(CSCs)CarcinomaCell cycle heterogeneityQuiescenceTherapy resistanceTherapy toleranceTumor dormancy

Ebrahim H.Maleki、Ahmad Reza Bahrami、Maryam M.Matin

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Department of Biology,Faculty of Science,Ferdowsi University of Mashhad,9177948974 Mashhad,Iran

Jagiellonian Centre for Experimental Therapeutics(JCET),Jagiellonian University,31-007 Krakow,Poland

Doctoral School of Exact and Natural Sciences,Jagiellonian University,30-348 Krakow,Poland

Industrial Biotechnology Research Group,Institute of Biotechnology,Ferdowsi University of Mashhad,9177948974 Mashhad,Iran

Novel Diagnostics and Therapeutics Research Group,Institute of Biotechnology,Ferdowsi University of Mashhad,9177948974 Mashhad,Iran

Stem Cell and Regenerative Medicine Research Group,Iranian Academic Center for Education,Culture and Research(ACECR),Khorasan Razavi Branch,917751376 Mashhad,Iran

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Ferdowsi University of Mashhad(FUM)

2024

10.1016/j.gendis.2022.11.025

基因与疾病(英文)

基因与疾病(英文)

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年,卷(期)：2024.11(1)
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