Novel therapeutics in combination with radiotherapy to improve cancer treatment: Rationale, mechanisms of action and clinical perspective

Verheij, Marcel; Vens, Conchita; van Triest, Baukelien

doi:10.1016/j.drup.2010.01.002

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Volume 13, Issue 1 , Pages 29-43, February 2010

Novel therapeutics in combination with radiotherapy to improve cancer treatment: Rationale, mechanisms of action and clinical perspective

Marcel Verheij
- Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
- Division of Experimental Therapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
- Corresponding author at: Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Tel.: +31 20 5122120; fax: +31 20 6691101.
Conchita Vens
- Division of Experimental Therapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Baukelien van Triest
- Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

Received 29 December 2009; received in revised form 21 January 2010; accepted 22 January 2010. published online 19 February 2010.

Abstract

Our increased understanding of the molecular processes underlying cellular sensitivity to ionizing radiation has led to the identification of novel targets for intervention. New agents have become available for combined use to overcome radioresistance and enhance the clinical efficacy of radiotherapy. This rational selection of potential radiosensitizers contrasts with the empirical approach that has dominated the field of chemo-radiotherapy over the last decades. It allows the identification of those patients who will benefit most from a specific combination by exploiting new predictive biomarkers of response. In this review we present several approaches of targeted radiosensitization and discuss the available in vitro and in vivo results that support their translation into clinical trials. We focus on EGFR-inhibiting, anti-angiogenic, apoptosis-modulating and PARP-interfering strategies.

Keywords: Radiotherapy, Radiosensitizer, EGFR inhibitors, Angiogenesis inhibitors, PARP inhibitors, Apoptosis targeting agents, Tyrosine kinase inhibitors, Response prediction