Abstract
Radiotherapy (RT) is part of standard cancer treatment. Innovations in treatment planning and increased precision in dose delivery have significantly improved the therapeutic gain of radiotherapy but are reaching their limits due to biologic constraints. Thus, a better understanding of the complex local and systemic responses to RT and of the biological mechanisms causing treatment success or failure is required if we aim to define novel targets for biological therapy optimization. Moreover, optimal treatment schedules and prognostic biomarkers have to be defined for assigning patients to the best treatment option. The complexity of the tumor environment and of the radiation response requires extensive in vivo experiments for the validation of such treatments. So far in vivo investigations have mostly been performed in time- and cost-intensive murine models. Here we propose the implementation of the chick chorioallantoic membrane (CAM) model as a fast, cost-efficient model for semi high-throughput preclinical in vivo screening of the modulation of the radiation effects by molecularly targeted drugs. This review provides a comprehensive overview on the application spectrum, advantages and limitations of the CAM assay and summarizes current knowledge of its applicability for cancer research with special focus on research in radiation biology and experimental radiation oncology.
Highlights
About 50% of all cancer patients receive radiotherapy (RT) at some point during the course of their disease (World Health Organization, WHO) and good results in terms of long-term survival and tumor cure are achieved in a variety of tumors by multimodal combinations of surgery, RT, and chemotherapy [1]
We propose the implementation of the chick chorioallantoic membrane (CAM) model as a fast, cost-efficient model for semi high-throughput preclinical in vivo screening of the modulation of the radiation effects by molecularly targeted drugs
On the basis of preclinical studies describing the CAM as a tumor stroma surrogate and propagating its applicability for experiments on tumor-stroma interaction and combinatorial treatments, we propose the CAM as a useful preclinical model for in vivo investigations of hypothesized synergistic effects of radiation–drug combinations
Summary
About 50% of all cancer patients receive radiotherapy (RT) at some point during the course of their disease (World Health Organization, WHO) and good results in terms of long-term survival and tumor cure are achieved in a variety of tumors by multimodal combinations of surgery, RT, and chemotherapy [1]. Cancers 2019, 11, 1499 the quality of life of cancer patients, whereas tolerable doses are often linked to suboptimal tumor control [3,4,5,6,7] These limitations highlight the high medical need for innovations in RT practice. Despite success, improving cure-rates through technical and physical improvements in accurate dose delivery has some natural limits defined by the biological characteristics of the tumor or the infiltration of critical normal-tissue structures by malignant cells that cannot be spared, further underlining the need for further innovation in radiotherapy practice
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