scholarly journals SOX2 in cancer stemness: tumor malignancy and therapeutic potentials

2018 ◽  
Vol 12 (2) ◽  
pp. 85-98 ◽  
Author(s):  
Mahfuz Al Mamun ◽  
Kaiissar Mannoor ◽  
Jun Cao ◽  
Firdausi Qadri ◽  
Xiaoyuan Song
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Epithelial To Mesenchymal Transition ◽  
Immune Surveillance ◽  
Resistance Mechanisms ◽  
Clinical Relapse ◽  
Cancer Therapies ◽  
Cancer Stemness ◽  
Mesenchymal Transition ◽  
Anti Cancer

Abstract Cancer stem cells (CSCs), a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors, posit a significant challenge to develop effective and long-lasting anti-cancer therapies. The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs, thereby leading to CSC-mediated clinical relapse. Accumulating evidence suggests that transcription factor SOX2, a master regulator of embryonic and induced pluripotent stem cells, drives cancer stemness, fuels tumor initiation, and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition, ATP-binding cassette drug transporters, anti-apoptotic and/or pro-survival signaling, lineage plasticity, and evasion of immune surveillance. Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.

scholarly journals The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Kate Dinneen ◽  
Anne-Marie Baird ◽  
Ciara Ryan ◽  
Orla Sheils
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Current Knowledge ◽  
Gastroesophageal Junction ◽  
Western World ◽  
Specific Cell ◽  
Cancer Therapies ◽  
Mesenchymal Transition ◽  
Anti Cancer

Gastroesophageal junction adenocarcinomas (GEJA) have dramatically increased in incidence in the western world since the mid-20th century. Their prognosis is poor, and conventional anti-cancer therapies do not significantly improve survival outcomes. These tumours are comprised of a heterogenous population of both cancer stem cells (CSC) and non-CSCs, with the former playing a crucial role in tumorigenesis, metastasis and importantly drug resistance. Due to the ability of CSCs to self-replicate indefinitely, their resistance to anti-cancer therapies poses a significant barrier to effective treatment of GEJA. Ongoing drug development programmes aim to target and eradicate CSCs, however their characterisation and thus identification is difficult. CSC regulation is complex, involving an array of signalling pathways, which are in turn influenced by a number of entities including epithelial mesenchymal transition (EMT), microRNAs (miRNAs), the tumour microenvironment and epigenetic modifications. Identification of CSCs commonly relies on the expression of specific cell surface markers, yet these markers vary between different malignancies and indeed are often co-expressed in non-neoplastic tissues. Development of targeted drug therapies against CSCs thus requires an understanding of disease-specific CSC markers and regulatory mechanisms. This review details the current knowledge regarding CSCs in GEJA, with particular emphasis on their role in drug resistance.

scholarly journals Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what?

Open Biology ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 120066 ◽  
Author(s):  
Piet Borst
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Epithelial To Mesenchymal Transition ◽  
Residual Disease ◽  
Cancer Drug ◽  
Multi Drug Resistance ◽  
Mesenchymal Transition ◽  
Cell Death Pathways ◽  
P Glycoprotein ◽  
Mouse Tumour

Although chemotherapy of tumours has scored successes, drug resistance remains the major cause of death of cancer patients. Initial treatment often leaves residual disease, from which the tumour regrows. Eventually, most tumours become resistant to all available chemotherapy. I call this pan-resistance to distinguish it from multi-drug resistance, usually describing resistance caused by upregulation of drug transporters, such as P-glycoprotein. In this review, I discuss mechanisms proposed to explain both residual disease and pan-resistance. Although plausible explanations are at hand for residual disease, pan-resistance is still a mystery. My conclusion is that it is time for a major effort to solve this mystery using the new genetically modified mouse tumour models that produce real tumours resembling cancer in human patients.

scholarly journals Cancer drug resistance induced by EMT: novel therapeutic strategies

2021 ◽  
Author(s):  
Javier De Las Rivas ◽  
Anamaria Brozovic ◽  
Sivan Izraely ◽  
Alba Casas-Pais ◽  
Isaac P. Witz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
Limiting Factors ◽  
Cancer Drug ◽  
Clinical Samples ◽  
Cancer Therapies ◽  
Mesenchymal Transition ◽  
Clinical Benefits

AbstractOver the last decade, important clinical benefits have been achieved in cancer patients by using drug-targeting strategies. Nevertheless, drug resistance is still a major problem in most cancer therapies. Epithelial-mesenchymal plasticity (EMP) and tumour microenvironment have been described as limiting factors for effective treatment in many cancer types. Moreover, epithelial-to-mesenchymal transition (EMT) has also been associated with therapy resistance in many different preclinical models, although limited evidence has been obtained from clinical studies and clinical samples. In this review, we particularly deepen into the mechanisms of which intermediate epithelial/mesenchymal (E/M) states and its interconnection to microenvironment influence therapy resistance. We also describe how the use of bioinformatics and pharmacogenomics will help to figure out the biological impact of the EMT on drug resistance and to develop novel pharmacological approaches in the future.

Marine Natural Products as a Promising Source of Therapeutic Compounds to Target Cancer Stem Cells

2020 ◽  
Vol 27 ◽  
Author(s):  
Catarina Vizetto-Duarte ◽  
Pedro Castelo Branco ◽  
Luísa Custódio
Keyword(s):  
Stem Cells ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Marine Natural Products ◽  
Epithelial To Mesenchymal Transition ◽  
Heart Diseases ◽  
The Body ◽  
Mesenchymal Transition ◽  
Anti Cancer ◽  
Promising Source

: Cancer is the world’s second leading cause of death after heart diseases, and involves abnormal cell growth at a primary site and the potential to spread to other parts of the body. Tumors are highly heterogeneous and consist of subgroups of cells with distinct characteristics. Of these, the cancer stem cells (CSC) niche plays a crucial role in driving the spread of the tumor and are thought to provide treatment resistance. CSC is a rare special population of cancer cells exhibiting high tumorigenic properties together with self-renewal and differentiation capability. CSC is not only linked with high tumor-initiating activity, but is also implicated in chemotherapeutic re-sistance, metastasis, epithelial to mesenchymal transition, and recurrence. Thereafter, novel ther-apeutic strategies targeting CSC are in need in order to improve long-term clinical outcome. The literature supports the evidence that marine natural compounds can exhibit antioxidant, antimitot-ic, anti-inflammatory, anti-biotic as well as anticancer activity. In this review, we will provide an insight into the relevance of selected marine natural products as a source of bioactive compounds with anti-cancer properties, and to target CSC, which may benefit the development of novel anti-cancer therapeutic strategies.

scholarly journals MiRNA-mediated EMT and CSCs in cancer chemoresistance

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Bing Dong ◽  
Shiyu Li ◽  
Shuangli Zhu ◽  
Ming Yi ◽  
Suxia Luo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Complex Process ◽  
Cancer Chemoresistance

AbstractCancer stem cells (CSCs) are a small group of cancer cells, which contribute to tumorigenesis and cancer progression. Cancer cells undergoing epithelial-to-mesenchymal transition (EMT) acquire the chemoresistant ability, which is regarded as an important feature of CSCs. Thus, there emerges an opinion that the generation of CSCs is considered to be driven by EMT. In this complex process, microRNAs (miRNAs) are found to play a key role. In order to overcome the drug resistance, inhibiting EMT as well as CSCs phenotype seem feasible. Thereinto, regulating the EMT- or CSCs-associated miRNAs is a crucial approach. Herein, we conduct this review to elaborate on the complicated interplay between EMT and CSCs in cancer chemoresistance, which is modulated by miRNAs. In addition, we elucidate the therapeutic strategy to overcome drug resistance through targeting EMT and CSCs.

scholarly journals Role of Calcium Homeostasis in Modulating EMT in Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1200
Author(s):  
Clark A. Jones ◽  
Lori A. Hazlehurst
Keyword(s):  
Drug Resistance ◽  
Poor Prognosis ◽  
Epithelial To Mesenchymal Transition ◽  
Immune Surveillance ◽  
Calcium Flux ◽  
Mesenchymal Transition ◽  
Physiological Processes ◽  
Future Drug ◽  
Migratory Cells

Calcium is essential for cells to perform numerous physiological processes. In cancer, the augmentation of calcium signaling supports the more proliferative and migratory cells, which is a characteristic of the epithelial-to-mesenchymal transition (EMT). By genetically and epigenetically modifying genes, channels, and entire signaling pathways, cancer cells have adapted to survive with an extreme imbalance of calcium that allows them to grow and metastasize in an abnormal manner. This cellular remodeling also allows for the evasion of immune surveillance and the development of drug resistance, which lead to poor prognosis in patients. Understanding the role calcium flux plays in driving the phenotypes associated with invasion, immune suppression, metastasis, and drug resistance remains critical for determining treatments to optimize clinical outcomes and future drug discovery.

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