Improving radiotherapy in cancer treatment: Promises and challenges

Helen H.W. Chen and Macus Tien Kuo _

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Oncotarget. 2017; 8:62742-62758. https://doi.org/10.18632/oncotarget.18409

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Helen H.W. Chen1 and Macus Tien Kuo1,2

1Division of Clinical Radiation Oncology, Department of Radiation Oncology, National Cheng Kung University Hospital, Department of Radiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

2Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Correspondence to:

Macus Tien Kuo, email: [email protected]

Helen H.W. Chen, email: [email protected]

Keywords: radiotherapy, DNA damage response, hypoxia, cancer genomics, immune check points

Received: February 03, 2017     Accepted: April 18, 2017     Published: June 08, 2017


Effective radiotherapy for cancer has relied on the promise of maximally eradicating tumor cells while minimally killing normal cells. Technological advancement has provided state-of-the-art instrumentation that enables delivery of radiotherapy with great precision to tumor lesions with substantial reduced injury to normal tissues. Moreover, better understanding of radiobiology, particularly the mechanisms of radiation sensitivity and resistance in tumor lesions and toxicity in normal tissues, has improved the treatment efficacy of radiotherapy. Previous mechanism-based studies have identified many cellular targets that can affect radiation sensitivity, notably reactive oxygen species, DNA-damaging response signals, and tumor microenvironments. Several radiation sensitizers and protectors have been developed and clinically evaluated; however, many of these results are inconclusive, indicating that improvement remains needed. In this era of personalized medicine in which patients’ genetic variations, transcriptome and proteomics, tumor metabolism and microenvironment, and tumor immunity are available. These new developments have provided opportunity for new target discovery. Several radiotherapy sensitivity-associated “gene signatures” have been reported although clinical validations are needed. Recently, several immune modifiers have been shown to associate with improved radiotherapy in preclinical models and in early clinical trials. Combination of radiotherapy and immunocheckpoint blockade has shown promising results especially in targeting metastatic tumors through abscopal response. In this article, we succinctly review recent advancements in the areas of mechanism-driven targets and exploitation of new targets from current radio-oncogenomic and radiation-immunotherapeutic approaches that bear clinical implications for improving the treatment efficacy of radiotherapy.

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