Cancer stem cells: the development of new cancer therapeutics

Scatena, Roberto; Bottoni, Patrizia; Pontoglio, Alessandro; Giardina, Bruno

doi:10.1517/14712598.2011.573780

Cited by 35 publications

(27 citation statements)

References 112 publications

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“…Second, with technological advances, the advent of personalized medicine will culminate with the development of therapies focused on the molecular identity of individual patients and tumors. The discovery and isolation of specific molecular signatures in the patient's tumor will allow for the selection of a more appropriate regimen of chemo- or radiotherapy [110]. Furthermore, in-depth analysis of intratumoral heterogeneity and GSC phenotype by single cell study will enable the identification of possible mechanisms by which the tumor evades standard therapies and acquires more aggressive features.…”

Section: What Does the Future Hold?mentioning

confidence: 99%

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Auffinger

Spencer

Pytel

et al. 2015

Expert Review of Neurotherapeutics

225

184

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Glioma stem cells (GSCs) constitute a slow-dividing, small population within a heterogeneous glioblastoma. They are able to self-renew, recapitulate a whole tumor, and differentiate into other specific GBM subpopulations. Therefore, they have been held responsible for malignant relapse after primary standard therapy and the poor prognosis of recurrent GBM. The failure of current therapies to eliminate specific GSC subpopulations has been considered a major factor contributing to the inevitable recurrence in GBM patients following treatment. Here, we discuss the molecular mechanisms of chemoresistance of GSCs and the reasons why complete eradication of GSCs is so difficult to achieve. We will also describe the targeted therapies currently available towards GSCs and possible mechanisms to overcome such chemoresistance and avoid therapeutic relapse.

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Section: What Does the Future Hold?mentioning

confidence: 99%

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Auffinger

Spencer

Pytel

et al. 2015

Expert Review of Neurotherapeutics

225

184

View full text Add to dashboard Cite

show abstract

“…CSCs typically survive anticancer drug treatment and self-renew to eventually reconstitute the entire tumor. 1−4 The recurrence of tumor is difficult to treat with traditional anticancer drugs that primarily target “bulk” cancer cells. A new approach is critically needed to prevent disease recurrence arising from inability to destroy CSCs.…”

mentioning

confidence: 99%

Synthetic, Non-saccharide, Glycosaminoglycan Mimetics Selectively Target Colon Cancer Stem Cells

et al. 2014

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Selective targeting of cancer stem-like cells (CSCs) is a paradigm-shifting approach. We hypothesized that CSCs can be targeted by interfering with functions of sulfated glycosaminoglycans, which play key roles in cancer cell growth, invasion and metastasis. We developed a tandem, dual screen strategy involving (1) assessing inhibition of monolayer versus spheroid growth and (2) assessing inhibition of primary versus secondary spheroid growth to identify G2.2, a unique sulfated nonsaccharide GAG mimetic (NSGM) from a focused library of 53 molecules, as a selective inhibitor of colon CSCs. The NSGM down-regulated several CSC markers through regulation of gene transcription, while closely related, inactive NSGMs G1.4 and G4.1 demonstrated no such changes. G2.2’s effects on CSCs were mediated, in part, through induction of apoptosis and inhibition of self-renewal factors. Overall, this work presents the proof-of-principle that CSCs can be selectively targeted through novel NSGMs, which are likely to advance fundamental understanding on CSCs while also aiding development of novel therapeutic agents.

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“…The imatinib-resistant variants of K562 showed several changes in levels of apoptosis-modulating molecules such as an increase in antiapoptotic Bcl-2 and Ku70 levels, and a decrease in proapoptotic Bax and Hsp70, which might be involved in the compensation for Bcr-Abl loss during the obtaining of imatinib resistance [28]. has not yet been seriously considered [37]. From the present study including two models of differentiation of K562 cells, …”

Section: Association Of Colony Forming Activity and Bcr-abl Expressiomentioning

confidence: 74%

“…Current failure with cancer treatment is not usually due to a lack of primary clinical responses including complete remission, but to recurrence or metastasis after initial therapies. The concept that cancer is driven by cancer-initiating or maintaining cells (popularly known as cancer stem cells, CSC) has recently attracted a great deal of attention [37]. While conventional cancer therapies have targeted well the bulk tumor cells, there is now compelling evidence that cancer-initiating cells may be responsible for recurrence or metastasis of cancers after successful initial induction of remission due to their resistance to traditional cancer treatments such as surgery, radiotherapy and chemotherapy [46].…”

Section: Introductionmentioning

confidence: 99%

Presence of Leukemia-maintaining Cells in Differentiation-resistant Fraction of K562 Chronic Myelogenous Leukemia

Lee¹,

Kim²,

Ha³

et al. 2013

Journal of Life Science

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The present study investigated whether leukemia-maintaining cells reside in a differentiation-resistant fraction using a megakaryocytic differentiation model of K562 cells. Treatment with phorbol-12-myristate-13-acetate (PMA) significantly inhibited the colony-forming efficiency of the K562 cells. At a PMA concentration of 1 nM or higher, colony was not formed, but approximately 40% of K562 cells still survived in soft agar. Approximately 70% of colony-forming cells that were isolated following the removal of PMA after exposure to the agent were differentiated after treatment with 10 nM PMA for 3 days. The differentiation rate of the colony-forming cells was gradually increased and reached about 90% 6 weeks after colony isolation, which was comparable to the level of a PMA-treated K562 control. Meanwhile, imatinib-resistant variants from the K562 cells, including K562/R1, K562/R2, and K562/R3 cells, did not show any colony-forming activity, and most imatinib-resistant variants were CD44 positive. After 4 months of culture in drug-free medium, the surface level of CD44 was decreased in comparison with primary imatinib-resistant variants, and a few colonies were formed from K562/R3 cells. In these cells, Bcr-Abl, which was lost in the imatinib-resistant variants, was re-expressed, and the original phenotypes of the K562 cells were partially recovered. These results suggest that leukemia-maintaining cells might reside in a differentiation-resistant population. Differentiation therapy to eliminate leukemia-maintaining cells could be a successful treatment for leukemia if the leukemia-maintaining cells were exposed to a differentiation inducer for a long time and at a high dose.

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Cancer stem cells: the development of new cancer therapeutics

Cited by 35 publications

References 112 publications

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Synthetic, Non-saccharide, Glycosaminoglycan Mimetics Selectively Target Colon Cancer Stem Cells

Presence of Leukemia-maintaining Cells in Differentiation-resistant Fraction of K562 Chronic Myelogenous Leukemia

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