Drug resistance and Cancer stem cells

Li, Yuan; Wang, Zhenning; Ajani, Jaffer A.; Song, Shumei

doi:10.1186/s12964-020-00627-5

Cited by 180 publications

(155 citation statements)

References 140 publications

(145 reference statements)

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“…In addition, CSCs express high levels of transmembrane transport proteins such as ATP-binding cassette transporters, which allow an increased efflux of chemotherapeutic agents out of the cells [ 23 ]. These proteins are usually located on the cell membrane and have the ability to export doxorubicin and methotrexate, among others [ 24 ]. CSC-mediated therapy resistance is also associated with avoidance of apoptosis through the rho family of proteins, non-coding RNAs, as well as stem cell niches—areas of tissue that provide specific microenvironments, which maintain and promote the CSCs’ capacity to self-renew and to generate differentiated progenies [ 23 , 24 ].…”

Section: Cancer Stem Cellsmentioning

confidence: 99%

Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy

et al. 2021

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Cancer stem cells (CSCs) are reportedly responsible for the initiation and propagation of cancer. Since CSCs are highly resistant to conventional chemo- and radiotherapy, they are considered the main cause of cancer relapse and metastasis. Salinomycin (Sali), an anticoccidial polyether antibiotic, has emerged as a promising new candidate for cancer therapy, with selective cytotoxicity against CSCs in various malignancies. Nanotechnology provides an efficient means of delivering Sali to tumors in view of reducing collateral damage to healthy tissues and enhancing the therapeutic outcome. This review offers an insight into the most recent advances in cancer therapy using Sali-based nanocarriers.

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Section: Cancer Stem Cellsmentioning

confidence: 99%

Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy

et al. 2021

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“…Drug resistance, which occurs in nearly all types of cancer, is a major problem in the treatment of cancer patients. Drug resistance can be classified in two ways-the intrinsic resistance, when tumors are resistant prior to treatment, and therefore, the drugs are not effective, even with initial early diagnosis and treatment, and acquired resistance, which occurs after prolonged cycles of chemotherapy, despite an initial positive response [1]. The intrinsic resistance includes aberrations of signals downstream or upstream of the targeted proteins leading to the acquisition of cancer hallmarks, while acquired resistance is inclined to preserve the original alterations and develop additional alterations that can adapt cancer cells to resist further drug treatments [2].…”

Section: Introductionmentioning

confidence: 99%

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

et al. 2021

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Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

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“…CSCs are rather refractory to most therapies and current drugs in clinical use [ 17 , 76 , 77 ], while most of the non-stem cell components of tumors could be eradicated. Thus, relapses and metastasis would be expected to occur if the drug-resistant CSC population remained intact, the latter being able to self-renew themselves and differentiate into heterogeneous lineages of cancer cells [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Induction of Apoptosis in Human Pancreatic Cancer Stem Cells by the Endoplasmic Reticulum-Targeted Alkylphospholipid Analog Edelfosine and Potentiation by Autophagy Inhibition

Gajate

Gayet

Fraunhoffer

et al. 2021

Cancers

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Pancreatic cancer is one of the most lethal malignancies with a poor and gloomy prognosis and the highest mortality-to-incidence ratio. Pancreatic cancer remains an incurable malignancy, and current therapies are ineffective. We isolated cancer stem cells (CSCs) from the human PANC-1 pancreatic cancer cell line as CD44+CD24+EpCAM+ cells. These CSCs form pancreatic cancer spheres or spheroids and develop tumors in SCID mice after subcutaneous injection of as few as 100 cells per mouse. Here, we found that the alkylphospholipid analog edelfosine inhibited CSC pancreatic cancer spheroid formation and induced cell death, as assessed by an increase in the percentage of cells in the sub-G0/G1 region by means of flow cytometry, indicative of DNA breakdown and apoptosis. This correlated with an increase in caspase-3 activity and PARP breakdown, as a major substrate of caspase-3, following PANC-1 CSC treatment with edelfosine. The antitumor ether lipid edelfosine colocalized with the endoplasmic reticulum in both PANC-1 cells as well as PANC-1 CSCs by using a fluorescent edelfosine analog, and induced an endoplasmic reticulum stress response in both PANC-1 cells and PANC-1 CSCs, with a potent CHOP/GADD153 upregulation. Edelfosine elicited a strong autophagy response in both PANC-1 cells and PANC-1 CSCs, and preincubation of CSCs with autophagy inhibitors, chloroquine or bafilomycin A1, enhanced edelfosine-induced apoptosis. Primary cultures from pancreatic cancer patients were sensitive to edelfosine, as well as their respective isolated CSCs. Nontumorigenic pancreatic human cell line HPNE and normal human fibroblasts were largely spared. These data suggest that pancreatic CSCs isolated from established cell lines and pancreatic cancer patients are sensitive to edelfosine through its accumulation in the endoplasmic reticulum and induction of endoplasmic reticulum stress.

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Drug resistance and Cancer stem cells

Cited by 180 publications

References 140 publications

Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy

Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Induction of Apoptosis in Human Pancreatic Cancer Stem Cells by the Endoplasmic Reticulum-Targeted Alkylphospholipid Analog Edelfosine and Potentiation by Autophagy Inhibition

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