Stem cells, cancer, and cancer stem cells

Reya, Tannishtha; Morrison, Sean J.; Clarke, Michael F.; Weissman, Irving L.

doi:10.1038/35102167

Cited by 8,456 publications

(7,331 citation statements)

References 77 publications

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“…Even when a complete radiologic response is observed, CSCs are still present and eventually lead to tumor regrowth 12. Therefore, targeting CSCs is a rational approach to preventing tumor regrowth and the development of resistance 12.…”

Section: Current Clinical Practice Guidelines and Treatment For Gastrmentioning

confidence: 99%

Identifying and targeting cancer stem cells in the treatment of gastric cancer

Bekaii‐Saab

El‐Rayes²

2017

Cancer

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Current treatment regimens for gastric cancer are not adequate. Cancer stem cells (CSCs) may be a key driving factor for growth and metastasis of this tumor type. In contrast to the conventional clonal evolution hypothesis, CSCs can initiate tumor formation, self‐renew, and differentiate into tumor‐propagating cells. Because gastric cancer can originate from CSCs, it is necessary to review current targets of signaling pathways for CSCs in gastric cancer that are being studied in clinical trials. These pathways are known to regulate the self‐renewal and differentiation process in gastric CSCs. A better understanding of the clinical results of trials that target gastric CSCs will lead to better outcomes for patients with gastric cancer. Cancer 2017;123:1303–1312. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Section: Current Clinical Practice Guidelines and Treatment For Gastrmentioning

confidence: 99%

Identifying and targeting cancer stem cells in the treatment of gastric cancer

Bekaii‐Saab

El‐Rayes²

2017

Cancer

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“…The 'stem cell model' of carcinogenesis suggests that cancers originate and are maintained by a rare fraction of cells called cancer stem cells (CSCs) (Reya et al, 2001;Pardal et al, 2003). These cells not only possess unique survival mechanisms but also harbor distinctive stem/progenitor cell properties including the ability to self-renew, differentiate and proliferate following a prolonged period of quiescence.…”

mentioning

confidence: 99%

CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway

et al. 2007

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The recent discovery of cancer stem cells (CSCs) has played a pivotal role in changing our view of carcinogenesis and chemotherapy. Based on this concept, CSCs are responsible for the formation and growth of neoplastic tissue and are naturally resistant to chemotherapy, explaining why traditional chemotherapies can initially shrink a tumor but fails to eradicate it in full, allowing eventual recurrence. Recently, we identified a CSC population in hepatocellular carcinoma (HCC) characterized by their CD133 phenotype. However, the molecular mechanism by which it escapes conventional therapies remains unknown. Here, we examined the sensitivity of these cells to chemotherapeutic agents (doxorubicin and fluorouracil) and the possible mechanistic pathway by which resistance may be regulated. Purified CD133 þ HCC cells isolated from human HCC cell line and xenograft mouse models survived chemotherapy in increased proportions relative to most tumor cells which lack the CD133 phenotype; the underlying mechanism of which required the preferential expression of survival proteins involved in the Akt/PKB and Bcl-2 pathway. Treatment of CD133 þ HCC cells with an AKT1 inhibitor, specific to the Akt/PKB pathway, significantly reduced the expression of the survival proteins that was normally expressed endogenously. In addition, treatment of unsorted HCC cells with both anticancer drugs in vitro significantly enriched the CD133 þ subpopulation.In conclusion, our results show that CD133 þ HCC cells contribute to chemoresistance through preferential activation of Akt/PKB and Bcl-2 cell survival response. Targeting of this specific survival signaling pathway in CD133 þ HCC CSCs may provide a novel therapeutic model for the disease.

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“…that equally affect all cells within a tumor [47]. The hierarchal model, on the other hand, holds that particular cells within a lineage are susceptible to transformation, and these self-renewing cells give rise to heterogeneous progeny [48, 49].…”

Section: Stem-like Basis For Human Malignanciesmentioning

confidence: 99%

Metastatic breast cancer cells in the bone marrow microenvironment: novel insights into oncoprotection

Patel

Dave²,

Murthy³

et al. 2010

Oncol Rev

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Among all cancers, malignancies of the breast are the second leading cause of cancer death in the United States after carcinoma of the lung. One of the major factors considered when assessing the prognosis of breast cancer patients is whether the tumor has metastasized to distant organs. Although the exact phenotype of the malignant cells responsible for metastasis and dormancy is still unknown, growing evidence has revealed that they may have stem cell-like properties that may account for resistance to chemotherapy and radiation. One process that has been attributed to primary tumor metastasis is the epithelial-to-mesenchymal transition. In this review, we specifically discuss breast cancer dissemination to the bone marrow and factors that ultimately serve to shelter and promote tumor growth, including the complex relationship between mesenchymal stem cells (MSCs) and various aspects of the immune system, carcinoma-associated fibroblasts, and the diverse components of the tumor microenvironment. A better understanding of the journey from the primary tumor site to the bone marrow and subsequently the oncoprotective role of MSCs and other factors within that microenvironment can potentially lead to development of novel therapeutic targets.

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Stem cells, cancer, and cancer stem cells

Cited by 8,456 publications

References 77 publications

Identifying and targeting cancer stem cells in the treatment of gastric cancer

Identifying and targeting cancer stem cells in the treatment of gastric cancer

CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway

Metastatic breast cancer cells in the bone marrow microenvironment: novel insights into oncoprotection

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