DNA repair: the culprit for tumor-initiating cell survival?

Mathews, Lesley; Cabarcas, Stephanie M.; Farrar, William L.

doi:10.1007/s10555-011-9277-0

Cited by 35 publications

(25 citation statements)

References 84 publications

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“…Oncomine analyses showed that numerous human cancers, such as of the prostate, brain, cervix, head and neck, kidney, bladder and pancreas, displayed elevated levels of DNA repair proteins [for review see ref. (154)]. Moreover, in melanoma, there is considerable evidence that DNA repair genes are upregulated in metastases compared with primary tumors (57, 155).…”

Section: Role Of Cell Cycle Checkpoint Control and Dna Repair Genes Imentioning

confidence: 99%

DNA Damage Response Genes and the Development of Cancer Metastasis

Broustas¹,

Lieberman²

2014

Radiation Research

237

159

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DNA damage response genes play vital roles in the maintenance of a healthy genome. Defects in cell cycle checkpoint and DNA repair genes, especially mutation or aberrant downregulation, are associated with a wide spectrum of human disease, including a predisposition to the development of neurodegenerative conditions and cancer. On the other hand, upregulation of DNA damage response and repair genes can also cause cancer, as well as increase resistance of cancer cells to DNA damaging therapy. In recent years, it has become evident that many of the genes involved in DNA damage repair have additional roles in tumorigenesis, most prominently by acting as transcriptional (co-) factors. Although defects in these genes are causally connected to tumor initiation, their role in tumor progression is more controversial and it seems to depend on tumor type. In some tumors like melanoma, cell cycle checkpoint/DNA repair gene upregulation is associated with tumor metastasis, whereas in a number of other cancers the opposite has been observed. Several genes that participate in the DNA damage response, such as RAD9, PARP1, BRCA1, ATM and TP53 have been associated with metastasis by a number of in vitro biochemical and cellular assays, by examining human tumor specimens by immunohistochemistry or by DNA genomewide gene expression profiling. Many of these genes act as transcriptional effectors to regulate other genes implicated in the pathogenesis of cancer. Furthermore, they are aberrantly expressed in numerous human tumors and are causally related to tumorigenesis. However, whether the DNA damage repair function of these genes is required to promote metastasis or another activity is responsible (e.g., transcription control) has not been determined. Importantly, despite some compelling in vitro evidence, investigations are still needed to demonstrate the role of cell cycle checkpoint and DNA repair genes in regulating metastatic phenotypes in vivo.

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Section: Role Of Cell Cycle Checkpoint Control and Dna Repair Genes Imentioning

confidence: 99%

DNA Damage Response Genes and the Development of Cancer Metastasis

Broustas¹,

Lieberman²

2014

Radiation Research

237

159

View full text Add to dashboard Cite

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“…Increased expression of major DNA repair proteins, including BRCA1, ATR and ATM, has been observed in pancreatic, breast and prostate CSCs [156][157][158]. Reduced DNA repair capacity in CSCs has also been reported (reviewed by Wang [159]).…”

Section: Dna Repairmentioning

confidence: 99%

Targeting therapy-resistant cancer stem cells by hyperthermia

Oei

Vriend

Krawczyk

et al. 2017

International Journal of Hyperthermia

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Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells (CSCs), is considered to be of particular significance for tumour initiation, progression and metastasis. CSCs are considered in particular to be therapy-resistant and may drive disease recurrence, which positions CSCs in the focus of anti-cancer research, but successful CSC-targeting therapies are limited. Here, we argue that hyperthermia -a therapeutic approach based on local heating of a tumour -is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising radiation and chemotherapy are least effective. Second, hyperthermia can modify factors that are essential for tumour survival and growth, such as the microenvironment, immune responses, vascularisation and oxygen supply. Third, hyperthermia targets multiple DNA repair pathways, which are generally upregulated in CSCs and protect them from DNA-damaging agents. Addition of hyperthermia to the therapeutic armamentarium of oncologists may thus be a promising strategy to eliminate therapy-escaping and -resistant CSCs.ARTICLE HISTORY

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“…When the DNA repair cascades are unable to adequately fix the damage, cell-cycle checkpoint components are activated which can recruit additional DNA repair components or activate apoptosis. Data from many studies imply that CSCs have elevated levels of DNA repair [53][54][55][56][57][58][59][60][61], these provide one explanation for the resistance of some tumor types to platinum agents.…”

Section: Chemoresistance Of Cancers Stem Cells By Enhanced Dna Repairmentioning

confidence: 99%

Chemoresistance in Cancer Stem Cells and Strategies to Overcome Resistance

Thomas¹,

Coyle²,

Sultan³

et al. 2014

Chemotherapy

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In cancers, there exists a subpopulation of cells which are referred to as cancer stem cells (CSCs) or tumor initiating cells that have enhanced tumor-initiating capacity and metastatic potential, and drive tumor progression. Since the initial identification of acute myeloid leukemia CSCs in 1997, CSCs have been found in many types of cancer and have intrinsic resistance to the current chemotherapeutic strategies. With increased levels of detoxifying enzymes, enhanced DNA repair abilities, impressive efflux capacity, and a slower cell-cycle; CSCs present a formidable obstacle against effective chemotherapy. Several methods of specifically targeting CSCs have been developed in recent years, and these compounds have potential as adjuvant therapies. The following is a review of the mechanisms responsible for chemoresistance in CSCs, with an emphasis on potential strategies to overcome this resistance.

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DNA repair: the culprit for tumor-initiating cell survival?

Cited by 35 publications

References 84 publications

DNA Damage Response Genes and the Development of Cancer Metastasis

DNA Damage Response Genes and the Development of Cancer Metastasis

Targeting therapy-resistant cancer stem cells by hyperthermia

Chemoresistance in Cancer Stem Cells and Strategies to Overcome Resistance

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