Title

New insights into the synergism of nucleoside analogs with radiotherapy

Authors

Authors

M. W. Lee; W. B. Parker;B. Xu

Comments

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Abbreviated Journal Title

Amer. Rev. Public Adm.

Keywords

Nucleoside analogs; Radiotherapy; Deoxycytidine kinase; ATM; CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN DEOXYCYTIDINE-KINASE; CELL; LUNG-CANCER; ADVANCED BREAST-CANCER; COLON-CARCINOMA CELLS; PHASE-II; TRIAL; PURINE ANALOGS; IN-VITRO; RIBONUCLEOTIDE REDUCTASE; PHOSPHORYLASE; DEFICIENCY; Oncology; Radiology, Nuclear Medicine & Medical Imaging

Abstract

Nucleoside analogs have been frequently used in combination with radiotherapy in the clinical setting, as it has long been understood that inhibition of DNA repair pathways is an important means by which many nucleoside analogs synergize. Recent advances in our understanding of the structure and function of deoxycytidine kinase (dCK), a critical enzyme required for the anti-tumor activity for many nucleoside analogs, have clarified the mechanistic role this kinase plays in chemo- and radio-sensitization. A heretofore unrecognized role of dCK in the DNA damage response and cell cycle machinery has helped explain the synergistic effect of these agents with radiotherapy. Since most currently employed nucleoside analogs are primarily activated by dCK, these findings lend fresh impetus to efforts focused on profiling and modulating dCK expression and activity in tumors. In this review we will briefly review the pharmacology and biochemistry of the major nucleoside analogs in clinical use that are activated by dCK. This will be followed by discussions of recent advances in our understanding of dCK activation via post-translational modifications in response to radiation and current strategies aimed at enhancing this activity in cancer cells.

Journal Title

Radiation Oncology

Volume

Radiat. Oncol.

Publication Date

1-1-2013

Document Type

Review

Language

English

First Page

10

WOS Identifier

8

ISSN

1748-717X

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