DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities DOI Open Access
Dana Jurkovičová, Christiana M. Neophytou, Ana Čipak Gašparović

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14672 - 14672

Published: Nov. 24, 2022

Resistance to chemo- and radiotherapy is a common event among cancer patients reason why new therapies therapeutic strategies need be in continuous investigation development. DNA damage response (DDR) comprises several pathways that eliminate maintain genomic stability integrity, but different types of cancers are associated with DDR machinery defects. Many improvements have been made recent years, providing drugs for patients, including those targeting the pathways. Currently, poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) (DDRi) approved cancers, breast, ovarian, pancreatic, prostate cancer. However, PARPi resistance growing issue clinical settings increases disease relapse aggravate patients’ prognosis. Additionally, other DDRi also being found investigated. The mechanisms include reversion mutations, epigenetic modification, stabilization replication fork, increased drug efflux. This review highlights therapy, its role conventional treatments, exploitation anticancer treatment. Biomarkers treatment response, combination agents, mechanisms, liabilities discussed.

Language: Английский

YTHDF1 Regulates Tumorigenicity and Cancer Stem Cell-Like Activity in Human Colorectal Carcinoma DOI Creative Commons
Yang Bai,

Chunxing Yang,

Runliu Wu

et al.

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: May 3, 2019

YTH N6-methyladenosine (m6A) RNA binding protein 1 (YTHDF1) is a core factor in methylation modification. Recent studies have shown that m6A closely related to multiple tumors, thus YTHDF1 may also play role tumorigenesis. This study, aimed explore the of colorectal cancer (CRC). In this we identified as being highly expressed at mRNA and levels TCGA, GEO CRC primary CRC. Furthermore, gene copy number was positively correlated with expression Knocking down significantly inhibited cell's tumorigenicity vitro murine xenograft tumor growth vivo. silencing colonosphere formation ability vitro. Mechanistically, found Wnt/β-catenin pathway activity cells. Together, overexpressed plays vital oncogenic CRC, novel finding provide potential therapeutic target for

Language: Английский

Citations

230
TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in colorectal cancer DOI Creative Commons
Qiang Tang, Jinhuang Chen,

Ziyang Di

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: Nov. 5, 2020

Abstract Background Transmembrane 4 L six family member 1 (TM4SF1) is upregulated in several epithelial cancers and closely associated with poor prognosis. However, the role of TM4SF1 its potential mechanism colorectal cancer (CRC) remain elusive. Methods We investigated expression Oncomine, Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases confirmed results by immunohistochemistry (IHC), qPCR Western blotting (WB) CRC tissues. The effect on epithelial-to-mesenchymal transition (EMT) stemness cells was Transwell, wound healing sphere formation assays. A series vitro vivo experiments were conducted to reveal mechanisms which modulates EMT CRC. Results markedly higher tissues than non-tumour positively correlated Downregulation inhibited migration, invasion tumour SW480 LoVo cells. Conversely, overexpression significantly enhanced tumoursphere cells, Additionally, silencing mediated transforming growth factor-β1 (TGF-β1). Mechanistically, gene set enrichment analysis (GSEA) predicted that Wnt signalling pathway one most impaired pathways TM4SF1-deficient compared controls. further validated WB, revealed modulated SOX2 a Wnt/β-catenin activation-dependent manner. Furthermore, we found knockdown suppressed c-Myc, leading decreased c-Myc binding promoter. Finally, depletion metastasis xenograft mouse model. Conclusion Our study substantiates novel maintains cell via Wnt/β-catenin/c-Myc/SOX2 axis during recurrence

Language: Английский

Citations

224
Emerging role of tumor cell plasticity in modifying therapeutic response DOI Creative Commons
Siyuan Qin, Jingwen Jiang, Yi Lü

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 7, 2020

Abstract Resistance to cancer therapy is a major barrier management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates key role non-mutational mechanisms underlying drug tolerance, the latter which focus will be discussed here. Such processes are largely driven by tumor cell plasticity, renders cells insusceptible drug-targeted pathway, thereby facilitating survival and growth. The concept plasticity highlights significance re-activation developmental programs closely correlated with epithelial–mesenchymal transition, properties stem cells, trans-differentiation potential during exposure. From observations in various cancers, this provides an opportunity for investigating nature anticancer resistance. Over years, our understanding emerging phenotype switching modifying therapeutic response has considerably increased. This expanded knowledge contributes developing novel strategies or combination regimens using available drugs, likely improve patient outcomes clinical practice.

Language: Английский

Citations

197
The Role of Cancer Stem Cells in Radiation Resistance DOI Creative Commons
C. Arnold, Julian Mangesius, Ira Skvortsova

et al.

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Feb. 20, 2020

Cancer stem cells (CSC) are a distinct subpopulation within tumor. They able to self-renew and differentiate possess high capability repair DNA damage, exhibit low levels of reactive oxygen species (ROS), proliferate slowly. These features render CSC resistant various therapies, including radiation therapy (RT). Eradication as many possible is requirement for an effective antineoplastic treatment therefore utmost importance the patient. This makes prime targets any therapeutic approach. Albeit clinical data still scarce, experimental first trials give hope that CSC-based has potential improve treatment, especially tumors known be resistant, such glioblastoma. In this review, we will discuss in context RT, describe mechanisms resistance, examine possibilities biomarkers, new approaches.

Language: Английский

Citations

188
Cyclodextrin-based delivery systems for chemotherapeutic anticancer drugs: A review DOI
Bingren Tian,

Shiyao Hua,

Jiayue Liu

et al.

Carbohydrate Polymers, Journal Year: 2019, Volume and Issue: 232, P. 115805 - 115805

Published: Dec. 30, 2019

Language: Английский

Citations

184
Nano-Based Approved Pharmaceuticals for Cancer Treatment: Present and Future Challenges DOI Creative Commons
Francisco Rodríguez, Pablo Caruana,

Noa De la Fuente

et al.

Biomolecules, Journal Year: 2022, Volume and Issue: 12(6), P. 784 - 784

Published: June 4, 2022

Cancer is one of the main causes death worldwide. To date, and despite advances in conventional treatment options, therapy cancer still far from optimal due to non-specific systemic biodistribution antitumor agents. The inadequate drug concentrations at tumor site led an increased incidence multiple resistance appearance many severe undesirable side effects. Nanotechnology, through development nanoscale-based pharmaceuticals, has emerged provide new innovative drugs overcome these limitations. In this review, we overview approved nanomedicine for rationale behind their designs applications. We also highlight approaches that are currently under investigation perspectives challenges nanopharmaceuticals, focusing on microenvironment disseminate cells as most attractive effective strategies treatments.

Language: Английский

Citations

162
Integration of multiomics data with graph convolutional networks to identify new cancer genes and their associated molecular mechanisms DOI
Roman Schulte-Sasse,

Stefan Budach,

Denes Hnisz

et al.

Nature Machine Intelligence, Journal Year: 2021, Volume and Issue: 3(6), P. 513 - 526

Published: April 12, 2021

Language: Английский

Citations

155
Cancer stem cell-targeted bio-imaging and chemotherapeutic perspective DOI
Jiyou Han, Miae Won, Ji Hyeon Kim

et al.

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 49(22), P. 7856 - 7878

Published: Jan. 1, 2020

Characteristics of CSCs targeted for developing therapeutic and bio-imaging agents.

Language: Английский

Citations

154
The role of polyphenols in overcoming cancer drug resistance: a comprehensive review DOI Creative Commons
Parisa Maleki Dana,

Fatemeh Sadoughi,

Zatollah Asemi

et al.

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: Jan. 3, 2022

Abstract Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading failure treatment and recurrence the disease. Polyphenols a family organic compounds with more than 10,000 members which have three-membered flavan ring system in common. These natural known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, modulating inflammation. Herein, we discuss role polyphenols (mainly curcumin, resveratrol, epigallocatechin gallate [EGCG]) different aspects drug resistance. Increasing uptake by tumor cells, metabolism enzymes (e.g. cytochromes glutathione-S-transferases), reducing efflux some mechanisms increase sensitivity cells chemotherapeutic agents. also affect other targets overcoming chemoresistance including cell death (i.e. autophagy apoptosis), EMT, ROS, DNA repair processes, stem epigenetics miRNAs).

Language: Английский

Citations

131
MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic DOI Creative Commons
Wen Li, Yunfei Wang, Ruifang Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 8, 2021

Overwhelming evidence indicates that virtually all treatment-naive tumors contain a subpopulation of cancer cells possess some stem cell traits and properties are operationally defined as (CSCs). CSCs manifest inherent heterogeneity in they may exist an epithelial proliferative state or mesenchymal non-proliferative invasive state. Spontaneous tumor progression, therapeutic treatments, (epi)genetic mutations also induce plasticity non-CSCs reprogram them into stem-like cells. Intrinsic induced plasticity, constantly dynamically, generate pool CSC subpopulations with varying levels epigenomic stability stemness. Despite the dynamic transient nature CSCs, play fundamental roles mediating therapy resistance relapse. It is now clear stemness coordinately regulated by genetic factors epigenetic mechanisms. Here, this perspective, we first provide brief updated overview CSCs. We then focus on microRNA-34a (miR-34a), tumor-suppressive microRNA (miRNA) devoid many advanced tumors. Being member miR-34 family, miR-34a was identified p53 target 2007. bona fide suppressor, its expression dysregulated downregulated various human cancers. By targeting such NOTCH, MYC, BCL-2, CD44, epigenetically negatively regulates functional shall briefly discuss potential reasons behind failure first-in-class clinical trial MRX34, liposomal mimic. Finally, offer several settings where can potentially be deployed to therapeutically advanced, therapy-resistant, p53-mutant order overcome curb

Language: Английский

Citations

125