Emerging role of tumor cell plasticity in modifying therapeutic response

Qin, Siyuan; Jiang, Jingwen; Lü, Yi; Nice, Edouard C.; Huang, Canhua; Zhang, Jian; Wang, He

doi:10.1038/s41392-020-00313-5

Cited by 169 publications

(138 citation statements)

References 685 publications

(1,106 reference statements)

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“…An integrative analysis of those classifications will provide a better understanding of GSCs. Multiple studies proved tumor cell adaptive survival from antitumor therapy, and this process was viewed as tumor therapeutic response 193 Therapy sensitive or resistant GSCs are also identified in each classification. For instance, MES GSCs, glutamine dependent GSCs and qGSCs show nature resistance to cancer therapy.…”

Section: Conclusion and Prospectionmentioning

confidence: 99%

The adaptive transition of glioblastoma stem cells and its implications on treatments

Wang

Zhang

et al. 2021

Sig Transduct Target Ther

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Glioblastoma is the most malignant tumor occurring in the human central nervous system with overall median survival time <14.6 months. Current treatments such as chemotherapy and radiotherapy cannot reach an optimal remission since tumor resistance to therapy remains a challenge. Glioblastoma stem cells are considered to be responsible for tumor resistance in treating glioblastoma. Previous studies reported two subtypes, proneural and mesenchymal, of glioblastoma stem cells manifesting different sensitivity to radiotherapy or chemotherapy. Mesenchymal glioblastoma stem cells, as well as tumor cells generate from which, showed resistance to radiochemotherapies. Besides, two metabolic patterns, glutamine or glucose dependent, of mesenchymal glioblastoma stem cells also manifested different sensitivity to radiochemotherapies. Glutamine dependent mesenchymal glioblastoma stem cells are more sensitive to radiotherapy than glucose-dependent ones. Therefore, the transition between proneural and mesenchymal subtypes, or between glutamine-dependent and glucose-dependent, might lead to tumor resistance to radiochemotherapies. Moreover, neural stem cells were also hypothesized to participate in glioblastoma stem cells mediated tumor resistance to radiochemotherapies. In this review, we summarized the basic characteristics, adaptive transition and implications of glioblastoma stem cells in glioblastoma therapy.

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Section: Conclusion and Prospectionmentioning

confidence: 99%

The adaptive transition of glioblastoma stem cells and its implications on treatments

Wang

Zhang

et al. 2021

Sig Transduct Target Ther

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“…A series of studies on various cancers highlight the contribution of CCL chemokine expression to the activation of EMT programs [ 104 ]. CCL2-mediated monocyte/macrophage trafficking was also observed in the inducible Kras G12D p53-null PDAC mouse model [ 33 ].…”

Section: Regulatory Effects Of the Tme And Its Cellular Componentsmentioning

confidence: 99%

Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness

Hass

Ohe

Ungefroren

2020

Cancers

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Tumor heterogeneity is considered the major cause of treatment failure in current cancer therapies. This feature of solid tumors is not only the result of clonal outgrowth of cells with genetic mutations, but also of epigenetic alterations induced by physical and chemical signals from the tumor microenvironment (TME). Besides fibroblasts, endothelial and immune cells, mesenchymal stroma/stem-like cells (MSCs) and tumor-associated macrophages (TAMs) intimately crosstalk with cancer cells and can exhibit both anti- and pro-tumorigenic effects. MSCs can alter cancer cellular phenotypes to increase cancer cell plasticity, eventually resulting in the generation of cancer stem cells (CSCs). The shift between different phenotypic states (phenotype switching) of CSCs is controlled via both genetic programs, such as epithelial-mesenchymal transdifferentiation or retrodifferentiation, and epigenetic alterations triggered by signals from the TME, like hypoxia, spatial heterogeneity or stromal cell-derived chemokines. Finally, we highlight the role of spontaneous cancer cell fusion with various types of stromal cells. i.e., MSCs in shaping CSC plasticity. A better understanding of cell plasticity and phenotype shifting in CSCs is a prerequisite for exploiting this phenomenon to reduce tumor heterogeneity, thereby improving the chance for therapy success.

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“…Individual cancer cells evolve with increasing genetic and phenotypic heterogeneity to a hierarchical organization whereby CSCs represent the top endowed with self-renewal capacity. The concept of tumor cell plasticity is also intimately connected to the reactivation of developmental programs that are closely correlated with EMT and transdifferentiation potential during drug exposure [50]. The impressive ability of tumor cells to switch their identities or phenotypes and stem cell state transitions may play a fundamental role in treatment escape.…”

Section: Cell Plasticity As Basis Of Intratumoral Heterogeneity and Dmentioning

confidence: 99%

“…Extrinsic components include the TME, injury, inflammation, viral infections, and drug treatment. A wide array of growth factors and their signaling pathways is involved in regulating cell plasticity, such as bone morphogenetic proteins, fibroblast growth factor, hepatocyte growth factor, Notch, platelet derived growth factor, sonic hedgehog, TGF-β, Wnt/β-catenin, and vascular endothelial growth factor [50].…”

Section: Factors Involved In Plasticity and Transdifferentiationmentioning

confidence: 99%

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

Hass

Ohe

Ungefroren

2020

Cancers

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Intratumoral heterogeneity is considered the major cause of drug unresponsiveness in cancer and accumulating evidence implicates non-mutational resistance mechanisms rather than genetic mutations in its development. These non-mutational processes are largely driven by phenotypic plasticity, which is defined as the ability of a cell to reprogram and change its identity (phenotype switching). Tumor cell plasticity is characterized by the reactivation of developmental programs that are closely correlated with the acquisition of cancer stem cell properties and an enhanced potential for retrodifferentiation or transdifferentiation. A well-studied mechanism of phenotypic plasticity is the epithelial-mesenchymal transition (EMT). Current evidence suggests a complex interplay between EMT, genetic and epigenetic alterations, and clues from the tumor microenvironment in cell reprogramming. A deeper understanding of the connections between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events is crucial to develop novel therapies that mitigate cell plasticity and minimize the evolution of tumor heterogeneity, and hence drug resistance. Alternatively, vulnerabilities exposed by tumor cells when residing in a plastic or stem-like state may be exploited therapeutically, i.e., by converting them into less aggressive or even postmitotic cells. Tumor cell plasticity thus presents a new paradigm for understanding a cancer’s resistance to therapy and deciphering its underlying mechanisms.

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Emerging role of tumor cell plasticity in modifying therapeutic response

Cited by 169 publications

References 685 publications

The adaptive transition of glioblastoma stem cells and its implications on treatments

The adaptive transition of glioblastoma stem cells and its implications on treatments

Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

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