Cancer cells with alternative lengthening of telomeres do not display a general hypersensitivity to ATR inhibition

Autor: Katharina I Deeg, Inn Chung, Caroline Bauer, Karsten Rippe
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Frontiers in Oncology, Vol 6 (2016)
Druh dokumentu: article
ISSN: 2234-943X
DOI: 10.3389/fonc.2016.00186
Popis: Telomere maintenance is a hallmark of cancer as it provides cancer cells with cellular immortality. A significant fraction of tumors uses the alternative lengthening of telomeres (ALT) pathway to elongate their telomeres and to gain an unlimited proliferation potential. Since the ALT pathway is unique to cancer cells, it represents a potentially valuable, currently unexploited target for anticancer therapies. Recently, it was proposed that ALT renders cells hypersensitive to ataxia telangiectasia- and RAD3-related (ATR) protein inhibitors (Flynn et al., Science 347, 273). Here, we measured the response of various ALT or telomerase positive cell lines to the ATR inhibitor VE-821. In addition, we compared the effect of the inhibitor on cell viability in isogenic cell lines, in which ALT was active or suppressed. In these experiments a general ATR inhibitor sensitivity of cells with ALT could not be confirmed. We rather propose that the observed variations in sensitivity reflect differences between cell lines that are unrelated to ALT.
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