Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation.

Authors

Giovanni L Gravina, Department of Experimental Medicine, Division of Radiation Oncology, S. Salvatore Hospital, L'Aquila, University of L'Aquila, Medical School, L'Aquila 67100, Italy; Department of Experimental Medicine, Laboratory of Radiobiology, University of L'Aquila, Medical School, L'Aquila 67100, Italy
Claudio Festuccia, Department of Experimental Medicine, Laboratory of Radiobiology, University of L'Aquila, Medical School, L'Aquila 67100, Italy
Francesco Marampon, Department of Cancer Biology and Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; Department of Experimental Medicine, Division of Radiation Oncology, S. Salvatore Hospital, L'Aquila, University of L'Aquila, Medical School, L'Aquila 67100, Italy; Department of Experimental Medicine, Laboratory of Radiobiology, University of L'Aquila, Medical School, L'Aquila 67100, ItalyFollow
Vladimir M Popov, Department of Cancer Biology and Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PAFollow
Richard G Pestell, Department of Cancer Biology and Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PAFollow
Bianca M Zani, Department of Experimental Medicine, Laboratory of Radiobiology, University of L'Aquila, Medical School, L'Aquila 67100, Italy
Vincenzo Tombolini, Department of Experimental Medicine, Division of Radiation Oncology, S. Salvatore Hospital, L'Aquila, University of L'Aquila, Medical School, L'Aquila 67100, Italy; Department of Experimental Medicine, Laboratory of Radiobiology, University of L'Aquila, Medical School, L'Aquila 67100, Italy

Document Type

Article

Publication Date

11-25-2010

Comments

This article has been peer reviewed and is published in Molecular Cancer 2010, 9:305. The published version is available at DOI: 10.1186/1476-4598-9-305. ©BioMed Central Ltd.

Abstract

Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic agents or radiation for targeting DNA-protein complex. The positive results obtained with these combined approaches in preclinical cancer models demonstrate the potential impact DNMT inhibitors may have in treatments of different cancer types. Therefore, as the emerging interest in use of DNMT inhibitors as a potential chemo- or radiation sensitizers is constantly increasing, further clinical investigations are inevitable in order to finalize and confirm the consistency of current observations.The present article will provide a brief review of the biological significance and rationale for the clinical potential of DNMT inhibitors in combination with other chemotherapeutics or ionizing radiation. The molecular basis and mechanisms of action for these combined treatments will be discussed herein.

Recommended Citation

Gravina, Giovanni L; Festuccia, Claudio; Marampon, Francesco; Popov, Vladimir M; Pestell, Richard G; Zani, Bianca M; and Tombolini, Vincenzo, "Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation." (2010). Kimmel Cancer Center Faculty Papers. Paper 9.
https://jdc.jefferson.edu/kimmelccfp/9

PubMed ID

21108789