Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies DOI Creative Commons
Jun He,

Zejing Qiu,

Jingjing Fan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 14, 2024

Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the tolerant persister (DTP) cell phenotype is attracting more and attention giving a predominant non-genetic role in cancer therapy The DTP characterized by quiescent or slow-cell-cycle reversible state subpopulation inert specialization to stimuli, which tolerates exposure some extent through interaction multiple underlying recovering growth proliferation after withdrawal, ultimately leading treatment resistance recurrence. Therefore, targeting cells anticipated provide new opportunities for patients, although our current knowledge these remains limited. In this review, we comprehensive overview formation characteristics cells, investigate potential drugs (including preclinical drugs, novel use old natural products) based on different medicine models, discuss necessity feasibility anti-DTP therapy, related application forms, future issues that will need be addressed advance emerging field towards clinical applications. Nonetheless, understanding functions may enable us develop effective improve outcomes patients.

Language: Английский

Gallbladder cancer DOI
Juan Carlos Roa, Patricia García, Vinay K. Kapoor

et al.

Nature Reviews Disease Primers, Journal Year: 2022, Volume and Issue: 8(1)

Published: Oct. 27, 2022

Language: Английский

Citations

193
Cancer cell plasticity during tumor progression, metastasis and response to therapy DOI
Andrea Pérez-González, Kevin Bévant, Cédric Blanpain

et al.

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(8), P. 1063 - 1082

Published: Aug. 3, 2023

Language: Английский

Citations

146
Mechanisms of cancer metastasis DOI Creative Commons
María Castañeda, Petra den Hollander, Nick A. Kuburich

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 87, P. 17 - 31

Published: Oct. 27, 2022

Metastatic cancer is almost always terminal, and more than 90% of deaths result from metastatic disease. Combating metastasis post-therapeutic recurrence successfully requires understanding each step progression. This review describes the current state knowledge etiology mechanism progression primary tumor growth to formation new tumors in other parts body. Open questions, avenues for future research, therapeutic approaches with potential prevent or inhibit through personalization patient's mutation and/or immune profile are also highlighted.

Language: Английский

Citations

126
Targeting Breast Cancer Stem Cells DOI Creative Commons
Lu Zhang, Wen‐Ming Chen, Suling Liu

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(2), P. 552 - 570

Published: Jan. 1, 2023

The potential roles of breast cancer stem cells (BCSCs) in tumor initiation and recurrence have been recognized for many decades.Due to their strong capacity self-renewal differentiation, BCSCs are the major reasons poor clinical outcomes low therapeutic response.Several hypotheses on origin proposed, including critical gene mutations cells, dedifferentiation somatic cell plasticity remodeling by epithelial-mesenchymal transition (EMT) microenvironment.Moreover, microenvironment, cellular components cytokines, modulates resistance BCSCs.Small molecules, antibodies, chimeric antigen receptor (CAR)-T targeting developed, applications combination with conventional therapies undergoing trials.In this review, we focus features BCSCs, emphasize factors environment that regulate stemness discuss BCSC-targeting therapies.

Language: Английский

Citations

112
Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies DOI Creative Commons
Zhenduo Shi, Kun Pang,

Zhuo‐Xun Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 11, 2023

Abstract Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed circumvent tumor plasticity, including epigenetic modifications, regulation transcription factors, activation suppression key signaling pathways, as well modification environment. Epithelial-to-mesenchymal transition, stem formation also serve roads towards Corresponding treatment strategies recently developed that either target plasticity-related employ combination treatments. In this review, we delineate plasticity its manipulation evasion from therapy. We discuss non-genetic drug-induced various types tumors provide insights into contribution acquired drug resistance. New therapeutic such inhibition reversal are presented. multitude clinical trials ongoing worldwide with intention improving outcomes. These advances direction for developing novel therapy regimens

Language: Английский

Citations

105
EMT mechanism in breast cancer metastasis and drug resistance: Revisiting molecular interactions and biological functions DOI Open Access
Mehrdad Hashemi, Hamid Zaferani Arani,

Sima Orouei

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113774 - 113774

Published: Oct. 3, 2022

One of the malignant tumors in women that has involved both developed and developing countries is breast cancer. Similar to other types tumors, cancer cells demonstrate high metastatic nature. Besides, tumor have ability drug resistance. EMT related mechanism metastasis focus current manuscript highlighting function malignancy Breast increase their migration by induction During EMT, N-cadherin vimentin levels increase, E-cadherin decrease mediate EMT-induced invasion. Different kinds anti-cancer agents such as tamoxifen, cisplatin paclitaxel mediates chemoresistance feature cells. Furthermore, correlates with radio-resistance tumor. Clinical aspect reversing preventing chemotherapy or radiotherapy failure patients improving survival time. The anti-tumor suppress can be used for decreasing invasion increasing chemosensitivity lncRNAs, miRNAs factors modulate progression are discussed here.

Language: Английский

Citations

99
WNT signaling and cancer stemness DOI Creative Commons

Masuko Katoh,

Masaru Katoh

Essays in Biochemistry, Journal Year: 2022, Volume and Issue: 66(4), P. 319 - 331

Published: July 15, 2022

Abstract Cancer stemness, defined as the self-renewal and tumor-initiation potential of cancer stem cells (CSCs), is a biology property featuring activation CSC signaling networks. Canonical WNT through Frizzled LRP5/6 receptors transmitted to β-catenin-TCF/LEF-dependent transcription machinery up-regulate MYC, CCND1, LGR5, SNAI1, IFNG, CCL28, CD274 (PD-L1) other target genes. causes expansion rapidly cycling CSCs modulates both immune surveillance tolerance. In contrast, noncanonical or ROR1/2 phospholipase C, Rac1 RhoA control transcriptional outputs mediated by NFAT, AP-1 YAP-TEAD, respectively. Noncanonical supports maintenance slowly cycling, quiescent dormant promotes epithelial–mesenchymal transition via crosstalk with TGFβ (transforming growth factor-β) cascades, while network induces evasion. The orchestrates functions cancer-associated fibroblasts, endothelial in tumor microenvironment fine-tunes stemness human cancers, such breast, colorectal, gastric lung cancers. Here, WNT-related features, including proliferation/dormancy plasticity, plasticity immune-landscape will be discussed. Porcupine inhibitors, β-catenin protein–protein interaction proteolysis targeting chimeras, ROR1 inhibitors ROR1-targeted biologics are investigational drugs cascades. Mechanisms regulated promising targets for therapeutic intervention; however, further understanding context-dependent reprogramming trajectories might necessary optimize clinical benefits WNT-targeted monotherapy applied combination therapy patients cancer.

Language: Английский

Citations

95
Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications DOI
Miguel A. Martín-Serrano, Benjamin Kepecs, Miguel Torres‐Martín

et al.

Gut, Journal Year: 2022, Volume and Issue: 72(4), P. 736 - 748

Published: May 18, 2022

Objective The diversity of the tumour microenvironment (TME) intrahepatic cholangiocarcinoma (iCCA) has not been comprehensively assessed. We aimed to generate a novel molecular iCCA classifier that incorporates elements stroma, and immune (‘STIM’ classification). Design applied virtual deconvolution transcriptomic data from ~900 iCCAs, enabling us devise classification by selecting for most relevant TME components. Murine models were generated through hydrodynamic tail vein injection compared with human disease. Results is composed five robust STIM classes encompassing both inflamed (35%) non-inflamed profiles (65%). classes, named classical (~10%) inflammatory stroma (~25%), differ in oncogenic pathways extent desmoplasia, showing T cell exhaustion, abundant KRAS mutations (p<0.001). Analysis cell–cell interactions highlights cancer-associated fibroblast subtypes as potential mediators evasion. Among desert-like class (~20%) harbours lowest infiltration regulatory cells (p<0.001), whereas hepatic stem-like (~35%) enriched ‘M2-like’ macrophages, IDH1/2 BAP1, FGFR2 fusions. remaining ( : ~10%) defined cycle poor prognosis. Comparative analysis unveils high similarity between KRAS/p19 murine model (p=0.02). KRAS-SOS inhibitor, BI3406, sensitises -mutant anti-PD1 therapy. Conclusions describe comprehensive TME-based stratification iCCA. Cross-species establishes align closely preclinical testing combination strategies.

Language: Английский

Citations

90
The epithelial–mesenchymal plasticity landscape: principles of design and mechanisms of regulation DOI
Jef Haerinck, Steven Goossens, Geert Berx

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(9), P. 590 - 609

Published: May 11, 2023

Language: Английский

Citations

71
FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions DOI

Masuko Katoh,

Yohann Loriot,

Giovanni Brandi

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(4), P. 312 - 329

Published: Feb. 29, 2024

Language: Английский

Citations

63