The developing cancer stem-cell model: clinical challenges and opportunities

Vermeulen, Louis; Melo, Felipe de Sousa e; Richel, Dick J.; Medema, Jan Paul

doi:10.1016/s1470-2045(11)70257-1

Cited by 347 publications

(290 citation statements)

References 73 publications

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“…Moreover, chemotherapy and radiation have been found to induce stemness genes in cancer cells, converting stemness-low cancer cells to stemness-high cancer cells (18,19). Such highly tumorigenic and drug-resistant stemness-high cancer stem cells are, therefore, likely to be "left over" after chemotherapy or radiotherapy and ultimately responsible for relapse (13,14,16,20,21). However, these stemness-high cancer stem cells are difficult to target owing to activation of prosurvival and antiapoptotic pathways, overexpression of drug efflux pumps, and increased DNA repair capacity (13,14,16,20,21).…”

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confidence: 99%

“…Such highly tumorigenic and drug-resistant stemness-high cancer stem cells are, therefore, likely to be "left over" after chemotherapy or radiotherapy and ultimately responsible for relapse (13,14,16,20,21). However, these stemness-high cancer stem cells are difficult to target owing to activation of prosurvival and antiapoptotic pathways, overexpression of drug efflux pumps, and increased DNA repair capacity (13,14,16,20,21). Therapeutic approaches based on the cancer stem cell hypothesis have centered on identifying specific cancer stem cell surface markers and the design of agents to selectively kill these marker-bearing cancer stem cells (22)(23)(24).…”

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confidence: 99%

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Suppression of cancer relapse and metastasis by inhibiting cancer stemness

Rogoff

Keates

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

410

366

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Partial or even complete cancer regression can be achieved in some patients with current cancer treatments. However, such initial responses are almost always followed by relapse, with the recurrent cancer being resistant to further treatments. The discovery of therapeutic approaches that counteract relapse is, therefore, essential for advancing cancer medicine. Cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential, drug sensitivity, and their potential to metastasize and cause relapse. Indeed, hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, that are highly tumorigenic and metastatic have been isolated from cancer patients with a variety of tumor types. Moreover, such stemness-high cancer cells are resistant to conventional chemotherapy and radiation. Here we show that BBI608, a small molecule identified by its ability to inhibit gene transcription driven by Stat3 and cancer stemness properties, can inhibit stemness gene expression and block spherogenesis of or kill stemnesshigh cancer cells isolated from a variety of cancer types. Moreover, cancer relapse and metastasis were effectively blocked by BBI608 in mice. These data demonstrate targeting cancer stemness as a novel approach to develop the next generation of cancer therapeutics to suppress cancer relapse and metastasis.cancer stemness | relapse | BBI608 C urrent cancer treatments ultimately fail owing to metastasis and relapse. Although chemotherapy can induce partial or even complete cancer regression in some patients, such initial responses are invariably followed by relapse, with the recurrent cancer being highly resistant to further chemotherapy, resulting in very limited survival benefits (1-3). Modern therapeutics designed to specifically target activating mutations are quite effective in inducing cancer regression in patients driven by such activating mutations; however, these treatments are also invariably followed by relapse with tumors that no longer respond to the targeted agent (2, 3). The discovery of novel therapeutic approaches that counteract cancer relapse is, therefore, urgently required for advancing cancer treatment.The idea that cancer is composed of a group of near-homogenous, ectopically growing cells has been replaced with a more complex model in which cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential to metastasize and cause relapse. The increased understanding of the genomic and proteomic complexity of tumor heterogeneity further highlights the extreme heterogeneity of cancer cells (4).Subpopulations of cancer cells with extremely high tumorigenic potential, termed cancer stem cells or stem-like cancer cells, have been isolated from cancer patients with a variety of tumor types (5-13) and found to have high stemness properties (5-15). Stemness, initially defined by the expression of stem cells genes, is a property shared by embryonic stem cells and adult stem cells (16). In ...

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confidence: 99%

mentioning

confidence: 99%

Suppression of cancer relapse and metastasis by inhibiting cancer stemness

Rogoff

Keates

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

410

366

View full text Add to dashboard Cite

show abstract

“…(21,38) This model therefore suggests that tumors are organized in a similar, albeit distorted, mannered as are their tissues of origin, and could potentially explain several phenomena that are currently incompletely understood. (39) According to the CSC model, minimal residual disease and tumor recurrence after treatment would be a result from remaining therapy-resistant CSC fraction, whereas metastatic potential would be a CSC-specific property. Although these hypotheses are appealing, they lack conclusive experimental evidence.…”

Section: Csc Conceptmentioning

confidence: 99%

Cancer Stem Cell Hypothesis: Implication for Cancer Prevention and Treatment

Meiliana

Dewi²,

Wijaya

2016

Indones Biomed J

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BACKGROUND: Cancer is a disease of genomic instability, evasion of immune cells, and adaptation of the tumor cells to the changing environment. Genetic heterogeneity caused by tumors and tumor microenvironmental factors forms the basis of aggressive behavior of some cancer cell populations.CONTENT: Cancers arise in self-renewing cell populations and that the resulting cancers, like their normal organ counterparts, are composed of hierarchically organized cell populations. Self – renewing “cancer stem cells” (CSC) maintain tumor growth and generate the diverse populations constituting the tumor bulk. CSCs in multiple tumor types have been demonstrated to be relatively resistant to radiation and chemotherapy. The clinical relevance of these studies has been supported by neoadjuvant breast cancer trials that demonstrated increases in the proportions of CSCs after therapy. The CSC hypothesis has tremendously important clinical implications.SUMMARY: In summary, a large and accumulating body of evidence supports the CSC hypothesis, which has important implications for cancer prevention and therapy. The ultimate test of this hypothesis will require clinical trials demonstrating that targeting of these pathways reduces cancer incidence and improves outcomes for patients with cancer.KEYWORDS: Somatic mutation, tumor heterogeneity, metastasis, epithelial-mesenchymal transition, CSC niche

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“…These cells are characterized by the ability to be immortalization, infiltrate and destroy normal tissues (Bjerkvig et al, 2005). Although cancer stem cell-like cells have been identified in many forms of cancer (Bjerkvig et al, 2005;Vermeulen et al, 2012), the identity of the normal cells that get the first genetic 'hits' leading to tumour initiation has remained unknown (Perez-Losada and Balmain, 2003). The origin of the cancer stem cells is still a scientific conundrum for the scientists.…”

Section: Cancer Stem Cellsmentioning

confidence: 99%

Hypothesis on the Role of Cytoplasmic "Short Base Sequences" in Carcinogenesis

Zhang

Xie²,

Tai³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Cancer is a highly complex medical problem with ramifications for public health throughout the world. Most studies have mainly focused on change in the nuclei as being aetiologically responsible. Few have examined the relationship between the cytoplasm and cancer, despite the fact that research has indicated that the cytoplasmic environment is an important factor for cellular differentiation and that the genetic information provided by the nucleus is entirely dependent on this environment for its expression. Gene mutations may be the result, rather than the cause of carcinogenesis. We submit a new concept -"short base sequences" (50-500 bps, including DNA or RNA sequences) in the cytoplasm which could play an important role in carcinogenesis. This is a new theory to explain the origin of the cancer.

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The developing cancer stem-cell model: clinical challenges and opportunities

Cited by 347 publications

References 73 publications

Suppression of cancer relapse and metastasis by inhibiting cancer stemness

Suppression of cancer relapse and metastasis by inhibiting cancer stemness

Cancer Stem Cell Hypothesis: Implication for Cancer Prevention and Treatment

Hypothesis on the Role of Cytoplasmic "Short Base Sequences" in Carcinogenesis

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