Circulating tumor cell markers for early detection and drug resistance assessment through liquid biopsy DOI Creative Commons

Priya Yadav,

R. Saravanan, Ramzi Hadj Lajimi

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 7, 2025

Circulating tumor cells (CTCs) are cancerous that extravasate from the primary or metastatic foci and travel through bloodstream to distant organs. CTCs provide crucial insights into cancer metastasis, evolution of genotypes during treatment, development chemo- and/or radio-resistance disease progression. The process Epithelial-to-mesenchymal transition (EMT) plays a key role in formation, as this enhances cell’s migration properties is often associated with increased invasiveness thereby leading chemotherapy resistance. During EMT process, lose epithelial markers like EpCAM acquire mesenchymal such vimentin driven by transcription factors Snail Twist. typically identified using specific cell surface markers, which vary depending on type. Common include EpCAM, used for cancers; CD44 CD24, stem cells; cytokeratins, CK8 CK18. Other HER2/neu can also be target types stages. Commonly, immune-based isolation techniques being implemented enrichment CTCs. This review emphasizes clinical relevance CTCs, particularly understanding drug resistance mechanisms, underscores importance EMT-derived multidrug (MDR). Moreover, discusses CTCs-specific their enrichment. Ultimately, EMT-specific found could significant information halt progression enable personalized therapies.

Язык: Английский

Expected and unexpected effects after systemic inhibition of Hippo transcriptional output in cancer DOI Creative Commons
Isabel Baroja, Nikolaos C. Kyriakidis, Georg Halder

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 27, 2024

Abstract Hyperactivation of YAP/TAZ, the Hippo pathway downstream effectors, is common in human cancer. The requirement YAP/TAZ for cancer cell survival preclinical models, prompted development pharmacological inhibitors that suppress their transcriptional activity. However, systemic inhibition may sometimes have unpredictable patient outcomes, with limited or even adverse effects because action not simply tumor promoting but also suppressive some types. Here, we review role distinct populations, discuss impact inhibiting output on growth, and examine current developments inhibitors.

Язык: Английский

Процитировано

17
Cancer plasticity in therapy resistance: Mechanisms and novel strategies DOI

Xing Niu,

Wenjing Liu,

Zhang Yinling

и другие.

Drug Resistance Updates, Год журнала: 2024, Номер 76, С. 101114 - 101114

Опубликована: Июнь 22, 2024

Язык: Английский

Процитировано

15
Regulating chemoresistance and cancer stemness: the CDH17-YAP pathway in distinct cellular states of lung cancer CTC clusters DOI Creative Commons
Zujun Que, Dan Qi,

Yun Jung Yang

и другие.

Cellular & Molecular Biology Letters, Год журнала: 2025, Номер 30(1)

Опубликована: Фев. 24, 2025

Abstract Background Drug resistance in metastatic lung cancer significantly contributes to patient mortality. This study explores the role of circulating tumor cells (CTCs), precursors metastasis, driving this resistance. We aim delineate unique biological traits CTC clusters and elucidate mechanisms underlying their chemotherapy. Methods used an ultralow adsorption plate establish a suspension culture system. Comparisons between adherent cultures CTC-TJH-01 were made via Cell Counting Kit-8 (CCK-8), western blot, immunofluorescence, flow cytometry assays evaluate cell proliferation, drug resistance, stemness. The tumorigenicity, growth rate, assessed nude mice. Transcriptomic proteomic analyses subsequently conducted identify differentially expressed genes proteins cultured under conditions. CDH17 gene knockdown was achieved through RNA interference, hematoxylin eosin (HE) staining, immunohistochemistry, immunofluorescence examine pathological status these cells. Results formed exhibited decreased growth, but increased stemness protein expression upregulated clusters, activating YAP/TAZ pathway. Knocking down not only inactivated pathway also proliferation activity cisplatin sensitivity clusters. Additionally, rate correlated with sensitivity. notably promoted xenografts enhanced cisplatin, although no significant difference observed compared those control group. Conclusions results indicate that stem cell-like properties exhibit chemoresistance, which is linked activated CDH17-YAP effectiveness primarily tumors relatively high rates, highlighting connection Graphical abstract

Язык: Английский

Процитировано

2
UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment DOI Creative Commons
Yin Li,

Manling Jiang,

Ling Aye

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 8, 2024

Abstract The complexity of the tumor microenvironment (TME) is a crucial factor in lung adenocarcinoma (LUAD) progression. To gain deeper insights into molecular mechanisms LUAD, we perform an integrative single-cell RNA sequencing (scRNA-seq) data analysis 377,574 cells from 117 LUAD patient samples. By linking scRNA-seq with bulk gene expression data, identify cluster prognostic-related UPP1 high cells. These cells, primarily situated at invasive front tumors, display stronger association immunosuppressive components TME. Our cytokine array reveals that upregulation leads to increased release various cytokines, TGF-β1 being particularly prominent. Furthermore, this also elevates PD-L1 through PI3K/AKT/mTOR pathway, which contributes suppression CD8 + T Cytometry by time-of-flight (CyTOF) provides additional evidence role shaping nature Using patient-derived organoids (PDOs), discover tumors exhibit relatively sensitivity Bosutinib and Dasatinib. Collectively, our study highlights these findings may provide features facilitate development personalized treatment strategies.

Язык: Английский

Процитировано

15
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities DOI
Mariangela Russo,

Mengnuo Chen,

Elisa Mariella

и другие.

Nature reviews. Cancer, Год журнала: 2024, Номер 24(10), С. 694 - 717

Опубликована: Сен. 2, 2024

Язык: Английский

Процитировано

11
The Cancer Antioxidant Regulation System in Therapeutic Resistance DOI Creative Commons

Xuanhao Gu,

Chunyang Mu,

Rujia Zheng

и другие.

Antioxidants, Год журнала: 2024, Номер 13(7), С. 778 - 778

Опубликована: Июнь 27, 2024

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cells adeptly maintain elevated levels both ROS and antioxidants through process termed "redox reprogramming". This balance optimizes proliferative influence while simultaneously reducing potential for cause damage cell. some cases, adapted antioxidant machinery can hamper efficacy treatments neoplastic diseases, representing significant facet resistance mechanisms observed therapy. this review, we outline contribution systems therapeutic resistance. We detail fundamental constituents these systems, encompassing central regulatory involving transcription factors (of particular importance is KEAP1/NRF2 signaling axis), molecular effectors antioxidants, auxiliary responsible NADPH generation. Furthermore, present recent clinical trials based on targeted treatment cancer, assessing as well challenges strategy Additionally, summarize pressing issues field, with aim illuminating path toward emergence novel anticancer approaches by orchestrating redox signaling.

Язык: Английский

Процитировано

9
Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies DOI Creative Commons
Jun He,

Zejing Qiu,

Jingjing Fan

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 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.

Язык: Английский

Процитировано

9
Single-cell RNA sequencing and machine learning provide candidate drugs against drug-tolerant persister cells in colorectal cancer DOI
Yosui Nojima, Ryoji Yao, Takashi Suzuki

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167693 - 167693

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
HDAC2‐Mediated METTL3 Delactylation Promotes DNA Damage Repair and Chemotherapy Resistance in Triple‐Negative Breast Cancer DOI Creative Commons
Xiaoniu He, Yuanpei Li, Jian Li

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Abstract The current treatment of triple‐negative breast cancer (TNBC) is still primarily based on platinum‐based chemotherapy. However, TNBC cells frequently develop resistance to platinum and experience relapse after drug withdrawal. It crucial specifically target eliminate cisplatin‐tolerant administration. Here, it reported that upregulated N 6 ‐methyladenosine (m A) modification drives the development in during cisplatin treatment. Mechanistically, histone deacetylase 2 (HDAC2) mediates delactylation methyltransferase‐like 3 (METTL3), facilitating METTL3 interaction with Wilms’‐tumor‐1‐associated protein subsequently increasing m A transcript‐associated DNA damage repair. This ultimately promotes cell survival under cisplatin. Furthermore, pharmacological inhibition HDAC2 using Tucidinostat can enhance sensitivity therapy. study not only elucidates biological function lactylated tumor but also highlights its negative regulatory effect resistance. Additionally, underscores nonclassical functional mechanism as a HDAC inhibitor for improving efficacy against TNBC.

Язык: Английский

Процитировано

1
Mitochondria‐Modulating Liposomes Reverse Radio‐Resistance for Colorectal Cancer DOI Creative Commons

Junmei Li,

Yuhong Wang,

Wenhao Shen

и другие.

Advanced Science, Год журнала: 2024, Номер 11(18)

Опубликована: Март 23, 2024

Complete remission of colorectal cancer (CRC) is still unachievable in the majority patients by common fractionated radiotherapy, leaving risks tumor metastasis and recurrence. Herein, clinical CRC samples demonstrated a difference phosphorylation translation initiation factor eIF2α (p-eIF2α) activating transcription 4 (ATF4), whose increased expression initial X-ray irradiation led to resistance subsequent radiotherapy. The underlying mechanism studied radio-resistant CT26 cells, revealing that incomplete mitochondrial outer membrane permeabilization (iMOMP) triggered key for elevated p-eIF2α ATF4, therefore radio-resistance. This finding guided discover metformin 2-DG are synergistic reversing radio inhibiting ATF4. Liposomes loaded with (M/D-Lipo) thus prepared enhancing radiotherapy CRC, which achieved satisfactory therapeutic efficacy both local metastatic tumors radio-resistance preventing T lymphocyte exhaustion.

Язык: Английский

Процитировано

6