Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: July 14, 2022

Abstract Background The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but also involved normal physiological processes adults. canonical regulates cell pluripotency determines the differentiation fate cells during development. (also known as Wnt/β-catenin pathway) recognized driver colon cancer one representative pathways. As functional effector molecule signaling, modification degradation β-catenin are key events progression cancer. Therefore, plays an important role pathogenesis diseases, especially colorectal (CRC). Objective Inhibit to explore therapeutic targets Methods Based on studying pathway, master biochemical related analyze relevant when drugs or inhibitors act clarify medication ideas for treatment Results pathways include: planar polarity (Wnt-PCP) Wnt-Ca 2+ pathway. closely proliferation, stemness, apoptosis, autophagy, metabolism, inflammation immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals molecular preparations CRC have now been developed. used clinically CRC. Conclusion drugs/phytochemicals targeting can effectively treat clinically.

Language: Английский

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The functional roles of the circRNA/Wnt axis in cancer

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: May 5, 2022

Abstract CircRNAs, covalently closed noncoding RNAs, are widely expressed in a wide range of species ranging from viruses to plants mammals. CircRNAs were enriched the Wnt pathway. Aberrant pathway activation is involved development various types cancers. Accumulating evidence indicates that circRNA/Wnt axis modulates expression cancer-associated genes and then regulates cancer progression. pathway-related circRNA obviously associated with many clinical characteristics. could regulate cell biological functions by interacting Moreover, circRNAs promising potential biomarkers for diagnosis, prognosis evaluation, treatment. In our review, we summarized recent research progress on role application tumorigenesis

Language: Английский

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Novel Insights on the Use of L-Asparaginase as an Efficient and Safe Anti-Cancer Therapy

Cancers, Journal Year: 2022, Volume and Issue: 14(4), P. 902 - 902

Published: Feb. 11, 2022

L-Asparaginase (L-ASNase) is an enzyme that hydrolyses the amino acid asparagine into aspartic and ammonia. Systemic administration of bacterial L-ASNase successfully used to lower bioavailability this non-essential eradicate rapidly proliferating cancer cells with a high demand for exogenous asparagine. Currently, it cornerstone drug in treatment most common pediatric cancer, acute lymphoblastic leukemia (ALL). Since these lymphoblasts lack expression synthetase (ASNS), depend on uptake extracellular survival. Interestingly, recent reports have illustrated may also clinical potential other aggressive subtypes hematological or solid cancers. However, immunogenic severe adverse side effects limit optimal use often lead discontinuation. The design optimized novel formulations provides opportunities overcome limitations. In addition, identification multiple resistance mechanisms, including ASNS promoter reactivation desensitization, has fueled research promising combinations chemoresistance. review, we discuss insights effects, both tumors, how variants can expand its applicability.

Language: Английский

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Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy

Molecular Biomedicine, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 4, 2022

Abstract Triple negative breast cancer (TNBC) is a subtype of cancer, with estrogen receptor, human epidermal growth factor receptor 2 and progesterone negative. TNBC characterized by high heterogeneity, rates metastasis, poor prognosis, lack therapeutic targets. Now the treatment still based on surgery chemotherapy, which effective only in initial stage but almost useless advanced stage. And due to hormone target, hormonal therapies have little beneficial effects. In recent years, signaling pathways receptor-specific targets been reported be patients under specific clinical conditions. targeted approved for many other cancers even subtypes options are limited. Most showed no response, may related heterogeneity TNBC, therefore more treatments predictive biomarkers needed. present review, we summarize potential opinions dysregulated receptors pathways, play significant role multiple stages development. We also focus application immunotherapy preclinical trials therapy TNBC. hope accelerate research development new drugs understanding relevant mechanisms, improve survival.

Language: Английский

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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(1), P. 103 - 134

Published: March 24, 2023

Wnt signaling plays a major role in regulating cell proliferation and differentiation. The ligands are family of 19 secreted glycoproteins that mediate their effects via binding to Frizzled receptors LRP5/6 coreceptors transducing the signal either through β-catenin canonical pathway or series other proteins noncanonical pathway. Many individual components both have additional functions throughout body, establishing complex interplay between pathways. This crosstalk pathways gives vital many cellular organ processes. Dysregulation this system has been implicated diseases affecting wide array systems, including cancer embryological defects, can even cause embryonic lethality. complexity its interacting made target for therapeutic treatments. However, stimulatory inhibitory treatments come with potential risks need be addressed. review synthesized much current knowledge on pathway, beginning history signaling. It thoroughly described different variants signaling, canonical, Wnt/PCP, Wnt/Ca2+ Further description involved each involvement Finally, explained various processes

Language: Английский

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A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 54, P. 271 - 292

Published: Feb. 14, 2023

Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of with associated chemoresistance. The development chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression membrane proteins (transporters), epigenetic changes, and alteration the cell signaling pathways/genes stem cells (CSCs). Due heterogeneous nature TNBC, therapeutic response existing modalities offers limited scope thus results in reccurance after therapy. To establish landmark efficacy, number novel have been proposed. In addition, reversal resistance that developed during treatment may altered by employing appropriate modalities. This review aims discuss plethora investigations carried out, which will help readers understand make an choice therapy directed toward complete elimination TNBC. manuscript addresses major contributory factors from microenvironment are responsible for chemoresistance poor prognosis. cellular events molecular mechanism-based interventions explained detail. Inhibition ABC transporters, pathways CSCs, modification promising this regard. TNBC progression, invasion, metastasis recurrence can also inhibited blocking multiple pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics generating reactive oxygen species (ROS).

Language: Английский

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Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 18, 2024

Abstract The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal conditions, the is meticulously regulated. However, aberrant activation of this downstream target genes can occur due to mutations key components pathway, epigenetic modifications, crosstalk with other pathways. Consequently, these dysregulations contribute significantly tumor initiation progression. Therapies targeting transduction have exhibited promising prospects potential for treatment. An increasing number medications are continuously being developed validated. This comprehensive review aims summarize latest advances our understanding played by carcinogenesis targeted therapy, providing valuable insights into acknowledging current opportunities challenges associated cancer research

Language: Английский

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Biomaterial‐Based In Situ Cancer Vaccines

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(43)

Published: Jan. 17, 2023

Cancer immunotherapies have reshaped the paradigm for cancer treatment over past decade. Among them, therapeutic vaccines that aim to modulate antigen-presenting cells and subsequent T cell priming processes are among first FDA-approved immunotherapies. However, despite showing benign safety profiles capability generate antigen-specific humoral cellular responses, been limited by modest efficacy, especially immunologically cold solid tumors. One key challenge lies in identification of tumor-specific antigens, which involves a costly lengthy process tumor isolation, DNA/RNA extraction, sequencing, mutation analysis, epitope prediction, peptide synthesis, antigen screening. To address these issues, situ actively pursued endogenous antigens directly from tumors utilize generated elicit potent cytotoxic lymphocyte (CTL) response. Biomaterials-based vaccines, particular, achieved significant progress taking advantage biomaterials can synergize adjuvants, troubleshoot delivery home, manipulate immune situ. This review will provide an overview biomaterials-based either living or artificial materials, under development clinic, discuss design criteria vaccines.

Language: Английский

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(3), P. 101026 - 101026

Published: July 22, 2023

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. proteins are secreted, lipid-modified molecules that activate the canonical (β-catenin dependent) non-canonical independent) pathways. Cellular behaviors such as proliferation, differentiation, maturation, proper body-axis specification carried out by pathway, which is best characterized of known paths. has emerged an important factor stem cell biology to affect self-renewal cells various tissues. This includes but not limited embryonic, hematopoietic, mesenchymal, gut, neural, epidermal cells. also been implicated tumor exhibit cell-like properties. crucial for bone formation presents potential target therapeutics disorders. Not surprisingly, aberrant associated with wide variety diseases, including cancer. Mutations members cancer can lead unchecked epithelial-mesenchymal transition, metastasis. Altogether, advances understanding dysregulated disease have paved way novel components pathway. Beginning brief overview mechanisms Wnt, this review aims summarize current knowledge cells, aberrations targeting preclinical clinical studies.

Language: Английский

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The role of RNA methylation in tumor immunity and its potential in immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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