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.

Non-coding RNAs as Novel Biomarkers in Cancer Drug Resistance

2021 ◽  
Vol 28 ◽  
Author(s):  
Haixiu Yang ◽  
Changlu Qi ◽  
Boyan Li ◽  
Liang Cheng
Keyword(s):  
Drug Resistance ◽  
Computational Methods ◽  
Cell Cycle Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Drug ◽  
Mesenchymal Transition ◽  
Treatment Regimens ◽  
Anticancer Treatment ◽  
Non Coding Rnas ◽  
Low Efficiency

: Chemotherapy is often the primary and most effective anticancer treatment; however, drug resistance remains a major obstacle to it being curative. Recent studies have demonstrated that non-coding RNAs (ncRNAs), especially microRNAs and long non-coding RNAs, are involved in drug resistance of tumor cells in many ways, such as modulation of apoptosis, drug efflux and metabolism, epithelial-to-mesenchymal transition, DNA repair, and cell cycle progression. Exploring the relationships between ncRNAs and drug resistance will not only contribute to our understanding of the mechanisms of drug resistance and provide ncRNA biomarkers of chemoresistance, but will also help realize personalized anticancer treatment regimens. Due to the high cost and low efficiency of biological experimentation, many researchers have opted to use computational methods to identify ncRNA biomarkers associated with drug resistance. In this review, we summarize recent discoveries related to ncRNA-mediated drug resistance and highlight the computational methods and resources available for ncRNA biomarkers involved in chemoresistance.

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.

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 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 Drug Resistance in Metastatic Breast Cancer: Tumor Targeted Nanomedicine to the Rescue

2021 ◽  
Vol 22 (9) ◽  
pp. 4673
Author(s):  
Vrinda Gote ◽  
Anantha Ram Nookala ◽  
Pradeep Kumar Bolla ◽  
Dhananjay Pal
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Metastatic Breast Cancer ◽  
Cancer Stem Cells ◽  
Metastatic Breast ◽  
Future Perspective ◽  
Cancer Drug ◽  
Breast Cancer Stem Cells ◽  
Mesenchymal Transition

Breast cancer, specifically metastatic breast, is a leading cause of morbidity and mortality in women. This is mainly due to relapse and reoccurrence of tumor. The primary reason for cancer relapse is the development of multidrug resistance (MDR) hampering the treatment and prognosis. MDR can occur due to a multitude of molecular events, including increased expression of efflux transporters such as P-gp, BCRP, or MRP1; epithelial to mesenchymal transition; and resistance development in breast cancer stem cells. Excessive dose dumping in chemotherapy can cause intrinsic anti-cancer MDR to appear prior to chemotherapy and after the treatment. Hence, novel targeted nanomedicines encapsulating chemotherapeutics and gene therapy products may assist to overcome cancer drug resistance. Targeted nanomedicines offer innovative strategies to overcome the limitations of conventional chemotherapy while permitting enhanced selectivity to cancer cells. Targeted nanotheranostics permit targeted drug release, precise breast cancer diagnosis, and importantly, the ability to overcome MDR. The article discusses various nanomedicines designed to selectively target breast cancer, triple negative breast cancer, and breast cancer stem cells. In addition, the review discusses recent approaches, including combination nanoparticles (NPs), theranostic NPs, and stimuli sensitive or “smart” NPs. Recent innovations in microRNA NPs and personalized medicine NPs are also discussed. Future perspective research for complex targeted and multi-stage responsive nanomedicines for metastatic breast cancer is discussed.

scholarly journals Current Perspectives on Phytomedicines targeting Cancer Stem Cells

2021 ◽  
Author(s):  
Mrunmayee Saraff ◽  
Rekha Gahtori ◽  
Surya Tripathi ◽  
Sugapriya Dhanasekaran ◽  
Sanjay Kumar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Efflux Pump ◽  
Cancer Drug ◽  
Molecular Signaling ◽  
Mesenchymal Transition ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Elevated Expression

Studies have established the presence of a small subpopulation of cells within tumor cells, known as cancer stem cells (CSCs). These cells have evidently been the reason for metastasis, chemotherapy or radiotherapy resistance and tumor relapses in several types of cancers. CSCs are prone to epithelial-to-mesenchymal transition (EMT), resulting in aggressive tumors. They modulate various pathways of molecular signaling, including Wnt, Hedgehog and Notch, thus increasing the stem-like characteristics. Elevated expression of ATP binding cassette (ABC) transporter efflux pump as well as suppression of apoptosis has also increased anti-cancer drug resistance. Plants are known to possess bioactive compounds that can modulate these key regulators and hence eliminate CSCs. This review aims to report and summarize preclinical studies about the effects of phytocompounds on CSCs of various tumors. Furthermore, clinical trials carried out for some of these phytoconstituents are reported. Thus, selectively targeting CSCs with plant extracts and herbal preparations may be a promising remedial strategy for cancer.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

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