Targeting cancer stem cell pathways for cancer therapy

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Фев. 7, 2020

Abstract Since cancer stem cells (CSCs) were first identified in leukemia 1994, they have been considered promising therapeutic targets for therapy. These self-renewal capacity and differentiation potential contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, OCT4, Sox2, Nanog, KLF4, MYC. In addition, many intracellular signaling pathways, Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers activators transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target rapamycin), TGF (transforming growth factor)/SMAD, PPAR (peroxisome proliferator-activated receptor), well extracellular vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, mesenchymal cells, matrix, exosomes, shown be very important regulators CSCs. Molecules, vaccines, antibodies, CAR-T (chimeric antigen receptor T cell) developed specifically CSCs, some these factors already undergoing clinical trials. This review summarizes the characterization identification depicts major pathways that regulate CSC development, discusses targeted therapy

Язык: Английский

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Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Авг. 7, 2020

The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, analysis cancer patients within pre- post-therapeutic period is required to identify several types cells, which carry a risk for disease progression subsequent relapse. Cancer stem cells (CSCs) are subpopulation tumor that can drive initiation cause relapses. At time point initiation, CSCs originate from either differentiated or adult tissue resident cells. Due their importance, characterize have been identified correlated prognosis. However, shown display high plasticity, changes phenotypic functional appearance. Such induced by chemo- radiotherapeutics as well senescent alterations microenvironment. Induction senescence causes shrinkage modulating an anti-tumorigenic environment undergo growth arrest immune attracted. Besides these positive effects after therapy, also negative displayed post-therapeutically. These unfavorable directly promote stemness CSC plasticity phenotypes, activating pathways non-CSCs, promoting escape activation pathways. end, all lead relapse metastasis. This review provides overview most frequently used markers implementation focussing on deadliest solid (lung, stomach, liver, breast colorectal cancers) hematological (acute myeloid leukemia, chronic leukemia) cancers. Furthermore, it gives examples how might be influenced therapeutics, such radiotherapy, It points out, crucial monitor residual CSCs, pro-tumorigenic senescence-associated secretory phenotype follow-up using specific biomarkers. As future perspective, targeted immune-mediated strategy chimeric antigen receptor based approaches removal remaining chemotherapy-resistant personalized therapeutic approach discussed.

Язык: Английский

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Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge

Cells, Год журнала: 2019, Номер 8(9), С. 957 - 957

Опубликована: Авг. 22, 2019

Triple-negative (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack treatment options. Chemotherapy remains standard care for TNBC treatment, but unfortunately, patients frequently develop resistance. Accordingly, in recent years, tremendous effort has been made into elucidating mechanisms chemoresistance with goal identifying new molecular targets. It become evident that development multifaceted based on elaborate interplay tumor microenvironment, drug efflux, stem cells, bulk cells. Alterations multiple signaling pathways govern these interactions. Moreover, TNBC’s highlighted existence several signatures, presents a significant obstacle successful treatment. In present, in-depth review, we explore contribution key as well emerging strategies overcome them. We discuss novel anti-tumor agents target components pay special attention their current clinical while emphasizing challenges still ahead management. The evidence presented this review outlines role crucial survival following chemotherapy highlights importance using combinatorial incorporating biomarkers studies.

Язык: Английский

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NF‐κB signaling in inflammation and cancer

MedComm, Год журнала: 2021, Номер 2(4), С. 618 - 653

Опубликована: Дек. 1, 2021

Abstract Since nuclear factor of κ‐light chain enhancer‐activated B cells (NF‐κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism NF‐κB for 35 years, which lead significant progress. Meanwhile, molecular mechanisms activation also illuminated, cascades signaling events leading activity key components pathway are identified. It has suggested plays an important role human diseases, especially inflammation‐related diseases. These studies make attractive target disease treatment. This review aims summarize knowledge family members NF‐κB, as well basic activation. We will effects dysregulated on inflammation, tumorigenesis, tumor microenvironment. The progression translational study drug development targeting inflammatory diseases cancer treatment potential obstacles be discussed. Further investigations precise functions physiological pathological settings underlying urgent need develop drugs treatment, with minimal side effects.

Язык: Английский

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Polymeric Nanoparticles for Drug Delivery

Chemical Reviews, Год журнала: 2024, Номер 124(9), С. 5505 - 5616

Опубликована: Апрель 16, 2024

The recent emergence of nanomedicine has revolutionized the therapeutic landscape and necessitated creation more sophisticated drug delivery systems. Polymeric nanoparticles sit at forefront numerous promising designs, due to their unmatched control over physiochemical properties such as size, shape, architecture, charge, surface functionality. Furthermore, polymeric have ability navigate various biological barriers precisely target specific sites within body, encapsulate a diverse range cargo efficiently release this in response internal external stimuli. However, despite these remarkable advantages, presence wider clinical application is minimal. This review will provide comprehensive understanding vehicles. affecting be outlined first, followed by description nanoparticle designs preparation methods, beginning with polymers on which they are based. meticulously explore current performance against myriad diseases including cancer, viral bacterial infections, before finally evaluating advantages crucial challenges that determine potential decades come.

Язык: Английский

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Deregulation of HLA-I in cancer and its central importance for immunotherapy

Journal for ImmunoTherapy of Cancer, Год журнала: 2021, Номер 9(8), С. e002899 - e002899

Опубликована: Авг. 1, 2021

It is now well accepted that many tumors undergo a process of clonal selection which means tumor antigens arising at various stages progression are likely to be represented in just subset cells. This thought driven by constant immunosurveillance applies selective pressure eliminating cells expressing recognized T becoming increasingly clear the same may also select for evade immune detection acquiring deficiencies their human leucocyte antigen (HLA) presentation pathways, allowing important persist within undetected system. Deficiencies pathway can arise variety mechanisms, including genetic and epigenetic changes, functional hard phenomenon assess using our standard analytical techniques. Nevertheless, it have profound clinical significance could define whether an individual patient will respond particular type therapy or not. In this review we consider mechanisms HLA function lost disease, implications current immunotherapy approaches checkpoint inhibitors examine prognostic impact loss demonstrated trials so far. Finally, propose strategies might explored possible stratification.

Язык: Английский

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Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1665 - 1665

Опубликована: Янв. 31, 2022

Triple-negative breast cancer (TNBC) is associated with high recurrence rates, incidence of distant metastases, and poor overall survival (OS). Taxane anthracycline-containing chemotherapy (CT) currently the main systemic treatment option for TNBC, while platinum-based showed promising results in neoadjuvant metastatic settings. An early arising intrinsic or acquired CT resistance common represents hurdle successful TNBC treatment. Numerous mechanisms were uncovered that can lead to development chemoresistance. These include stem cells (CSCs) induction after (NACT), ATP-binding cassette (ABC) transporters, hypoxia avoidance apoptosis, single factors such as tyrosine kinase receptors (EGFR, IGFR1), a disintegrin metalloproteinase 10 (ADAM10), few pathological molecular pathways. Some biomarkers capable predicting specific chemotherapeutic agents identified are expected be validated future studies more accurate selection drugs employed tailored approach, both advanced Recently, based on biomarkers, some therapies subsets became available clinical practice: olaparib talazoparib BRCA1/2 germline mutation carriers larotrectinib entrectinib neurotrophic tropomyosin receptor (NTRK) gene fusion carriers, anti-trophoblast cell surface antigen 2 (Trop2) antibody drug conjugate therapy heavily pretreated (mTNBC). Further targeting pathologic pathways, miRNAS, epidermal growth factor (EGFR), insulin 1 (IGF-1R), androgen (AR) under investigation. Among them, phosphatidylinositol 3 (PI3K)/protein B (Akt)/mammalian target rapamycin (mTOR) EGFR inhibitors well antiandrogens evaluation Phase II/III trials. Emerging allow select antiblastics alone by integrating conventional therapeutic approach may overcome/hinder

Язык: Английский

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Unveiling the mechanisms and challenges of cancer drug resistance

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Фев. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Язык: Английский

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miRNAs role in bladder cancer pathogenesis and targeted therapy: Signaling pathways interplay – A review

Pathology - Research and Practice, Год журнала: 2023, Номер 242, С. 154316 - 154316

Опубликована: Янв. 20, 2023

Язык: 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, Год журнала: 2023, Номер 54, С. 271 - 292

Опубликована: Фев. 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).

Язык: Английский

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