DNA topoisomerase I-targeting drugs as radiation sensitizers

Allan Y. Chen, Hak Choy, Mace L. Rothenberg

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Combination chemoradiation, alone or as an adjuvant to surgery, has been shown to improve treatment outcomes in a number of human malignancies, but may be limited by normal tissue toxicities. A primary challenge in radiation oncology is the development of drugs that can selectively enhance the cytotoxicity of ionizing radiation against tumor cells. Mammalian DNA topoisomerase I is the major cytotoxic target of a number of newly developed anticancer drugs that have shown efficacy against solid tumors, including colon cancer, ovarian cancer, lung cancer, cancer of the head and neck, and pediatric cancers. Topoisomerase I-targeting drugs exert their cytotoxic effect by producing enzyme-mediated DNA damage, rather than by directly inhibiting enzyme catalytic activity. DNA topoisomerase I recently has been established as a biochemical mediator of radiosensitization in cultured mammalian cells by camptothecin derivatives. Interestingly, this sensitization appears to be schedule-dependent, cell cycle phase-specific, cell line-dependent, and not strictly dependent on drug cytotoxicity. Clinical chemoradiation trials using camptothecin derivatives are currently ongoing. Future studies aimed at better understanding the underlying mechanisms of molecular radiosensitization with topoisomerase I-targeting drugs are pivotal to the clinical application of these agents, as well as in guiding the development of more effective radiosensitizers.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalOncology
Volume13
Issue number10 SUPPL. 5
StatePublished - 1999

Fingerprint

Radiation-Sensitizing Agents
Type I DNA Topoisomerase
Drug Delivery Systems
Camptothecin
Head and Neck Neoplasms
Lung Neoplasms
Pharmaceutical Preparations
Neoplasms
Radiation Oncology
Enzymes
Ionizing Radiation
Ovarian Neoplasms
Colonic Neoplasms
DNA Damage
Cultured Cells
Appointments and Schedules
Cell Cycle
Clinical Trials
Pediatrics
Cell Line

ASJC Scopus subject areas

  • Oncology

Cite this

Chen, A. Y., Choy, H., & Rothenberg, M. L. (1999). DNA topoisomerase I-targeting drugs as radiation sensitizers. Oncology, 13(10 SUPPL. 5), 39-46.

DNA topoisomerase I-targeting drugs as radiation sensitizers. / Chen, Allan Y.; Choy, Hak; Rothenberg, Mace L.

In: Oncology, Vol. 13, No. 10 SUPPL. 5, 1999, p. 39-46.

Research output: Contribution to journalArticle

Chen, AY, Choy, H & Rothenberg, ML 1999, 'DNA topoisomerase I-targeting drugs as radiation sensitizers', Oncology, vol. 13, no. 10 SUPPL. 5, pp. 39-46.
Chen AY, Choy H, Rothenberg ML. DNA topoisomerase I-targeting drugs as radiation sensitizers. Oncology. 1999;13(10 SUPPL. 5):39-46.
Chen, Allan Y. ; Choy, Hak ; Rothenberg, Mace L. / DNA topoisomerase I-targeting drugs as radiation sensitizers. In: Oncology. 1999 ; Vol. 13, No. 10 SUPPL. 5. pp. 39-46.
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