Abstract：
:Complete and accurate DNA replication is fundamental to cellular proliferation and genome stability. Obstacles that delay, prevent, or terminate DNA replication cause the phenomena termed DNA replication stress. Cancer cells exhibit chronic replication stress due to the loss of proteins that protect or repair stressed replication forks and due to the continuous proliferative signaling, providing an exploitable therapeutic vulnerability in tumors. Here, we outline current and pending therapeutic approaches leveraging tumor-specific replication stress as a target, in addition to the challenges associated with such therapies. We discuss how replication stress modulates the cell-intrinsic innate immune response and highlight the integration of replication stress with immunotherapies. Together, exploiting replication stress for cancer treatment seems to be a promising strategy as it provides a selective means of eliminating tumors, and with continuous advances in our knowledge of the replication stress response and lessons learned from current therapies in use, we are moving toward honing the potential of targeting replication stress in the clinic.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Ubhi T,Brown GWdoi
10.1158/0008-5472.CAN-18-3631subject
Has Abstractpub_date
2019-04-15 00:00:00pages
1730-1739issue
8eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-18-3631journal_volume
79pub_type
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