Cancer stem cells: Road to therapeutic resistance and strategies to overcome resistance

Makena, Monish R.; Ranjan, Alok; Thirumala, Vani; Reddy, Arubala P.

doi:10.1016/j.bbadis.2018.11.015

Cited by 93 publications

(90 citation statements)

References 139 publications

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“…These Cancer Stem Cells (CSCs) give rise to shorter-lived malignant cells that make up the bulk of the tumor. At the same time, they are able to sustain long-term tumor growth thanks to their self-renewal ability and their increased resistance to chemotherapy and radiotherapy [46,47]. Moreover, CSCs are thought to be primarily responsible for tumor relapse [46,47].…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, they are able to sustain long-term tumor growth thanks to their self-renewal ability and their increased resistance to chemotherapy and radiotherapy [46,47]. Moreover, CSCs are thought to be primarily responsible for tumor relapse [46,47]. Although solid evidence supports such a hierarchical organization in many tumor types, it is not clear whether this would apply to all cancer types [48].…”

Section: Discussionmentioning

confidence: 99%

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Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Pagella

Catón

Meisel

et al. 2020

Cells

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Ameloblastomas are locally invasive and aggressive odontogenic tumors treated via surgical resection, which results in facial deformity and significant morbidity. Few studies have addressed the cellular and molecular events of ameloblastoma onset and progression, thus hampering the development of non-invasive therapeutic approaches. Tumorigenesis is driven by a plethora of factors, among which innervation has been long neglected. Recent findings have shown that innervation directly promotes tumor progression. On this basis, we investigated the molecular characteristics and neurotrophic properties of human ameloblastomas. Our results showed that ameloblastomas express dental epithelial stem cell markers, as well as components of the Notch signaling pathway, indicating persistence of stemness. We demonstrated that ameloblastomas express classical stem cell markers, exhibit stem cell potential, and form spheres. These tumors express also molecules of the Notch signaling pathway, fundamental for stem cells and their fate. Additionally, we showed that ameloblastomas express the neurotrophic factors NGF and BDNF, as well as their receptors TRKA, TRKB, and P75/NGFR, which are responsible for their innervation by trigeminal axons in vivo. In vitro studies using microfluidic devices showed that ameloblastoma cells attract and form connections with these nerves. Innervation of ameloblastomas might play a key role in the onset of this malignancy and might represent a promising target for non-invasive pharmacological interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Pagella

Catón

Meisel

et al. 2020

Cells

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“…Notably, oncomiR‐21 can be as an activator for CAFs in TME (Nouraee et al, ). Sorafenib and sunitinib are other two FDA approved drugs to target the vascular endothelial growth factor receptors (VEGFRs) (Makena, Ranjan, Thirumala, & Reddy, ). Both the drugs reduce both tumor angiogenesis and cell proliferation at the same time because, in addition to VEGFRs, they also inhibit platelet‐derived growth factor receptors and receptor tyrosine kinase, which play a role in cell proliferation (Keating & Santoro, ).…”

Section: Targeting Ccscsmentioning

confidence: 99%

“…Notably, oncomiR-21 can be as an activator for CAFs in TME (Nouraee et al, 2013). Sorafenib and sunitinib are other two FDA approved drugs to target the vascular endothelial growth factor receptors (VEGFRs) (Makena, Ranjan, Thirumala, & Reddy, 2018).…”

Section: T a B L E 3 Targeting Ccscs' Cell Surface Moleculesmentioning

confidence: 99%

“…Despite many optimizations in targeting CCSCs and also other CSCs, cancer scientists still need to deal with a lot of challenges in making a full effective therapy for colon cancer. It is noteworthy that most of the different types of CSCs have a few shared deregulated stemness signaling pathways and also cell surface markers; however, blocking these markers and pathways have not yet given effective treatment in different cancers (Makena, Ranjan, Thirumala, & Reddy, 2018). In this case, one suggested the reason is that CSCs from different cancers may have different mechanisms of drug resistance and therefore, each cancer type may need a unique therapy (Kozovska, Gabrisova, & Kucerova, 2014 (Patel, Fong, & Jagosky, 2019).…”

Section: Future/potential Researchmentioning

confidence: 99%

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Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment

Jahanafrooz

Mosafer

Akbari

et al. 2019

Journal Cellular Physiology

115

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Despite many advances and optimization in colon cancer treatment, tumor recurrence and metastases make the development of new therapies necessary.Colon cancer stem cells (CCSCs) are considered as the main triggering factor of cancer progression, recurrence, and metastasis. CCSCs as a result of accumulated genetic and epigenetic alterations and also complex interconnection with the tumor microenvironment (TME) can evolve and convert to full malignant cells. Mounting evidence suggests that in cancer therapy both CCSCs and non-CCSCs in TME have to be regarded to break through the limitation of current therapies. In this regard, stem cell capabilities of some non-CCSCs may arise inside the TME condition. Therefore, a deep knowledge of regulatory mechanisms, heterogeneity, specific markers, and signaling pathways of CCSCs and their interconnection with TME components is needed to improve the treatment of colorectal cancer and the patient's life quality. In this review, we address current different targeted therapeutic options that target cell surface markers and signaling pathways of CCSCs and other components of TME.Current challenges and future perspectives of colon cancer personalized therapy are also provided here. Taken together, based on the deep understanding of biology of CCSCs and using three-dimensional culture technologies, it can be possible to reach successful colon cancer eradication and improvise combination targeted therapies against CCSCs and TME. K E Y W O R D Scolon cancer stem cells, colorectal cancer, combination therapy, complex interaction, signaling pathways, tumor microenvironment

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Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer

Zhang

Zhao

2021

Cancer Medicine

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Mining databases and data obtained from assays on human specimens had shown that Fzd7 is closely associated with Wnt7b, that Fzd7/Wnt7b expression is upregulated in pancreatic cancer tissues compared with normal tissues, and its expression is negatively correlated with survival. Fzd7/Wnt7b knockdown in Capan‐2 and Panc‐1 cells reduced the proliferative capacity of pancreatic cancer stem cells (PCSCs), reduced drug resistance, decreased the percentage of CD24+CD44+ subset of cells and the levels of ABCG2, inhibited cell‐sphere formation, and reduced gemcitabine (GEM) resistance. In contrast, Fzd7/Wnt7b overexpression increased the percentage of the CD24+CD44+ subset of cells, and increased the levels of ABCG2 detected in cell spheroids. The gem‐resistant cells exhibited higher levels of Fzd7/Wnt7b expression, an increased percentage of CD24+CD44+ cells, and higher levels of ABCG2 compared with the parental cells. Taken together, Fzd7/Wnt7b knockdown can reduce PDAC cell stemness and chemoresistance by reducing the percentage of CSCs. Mechanistically, Fzd7 binds with Wnt7b and modulates the levels of β‐catenin, and they may exert their role via modulation of the canonical Wnt pathway.

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Cancer stem cells: Road to therapeutic resistance and strategies to overcome resistance

Cited by 93 publications

References 139 publications

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment

Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer

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