Abstract
2656
Introduction: In the era of personalized oncology, pharmacogenomics and radiogenomics profiling are anticipated to play critical roles. Pharmacogenomics is deployed more on drug discovery efforts while radiogenomics data have opened new horizons for more effective radiotherapies in terms of optimized probability of tumor control and normal tissue complications. In the present educational exhibit, we emphasize the role of radiopharmacogenomics guided radiopharmaceutical therapy (RPG-RPT) based on a systems biology approach.
Methods: In RPT, two distinct factors impact the outcome: 1) radiobiology, because the effect of the therapy is caused by the ionizing radiation originating from the radioactive decay of the radionuclide and 2) pharmacokinetics, because the molecular characteristics of the pharmaceuticals and the interaction with different tissue is what defines how much radiation dose will be delivered to different organs and tumors. Given that different types of genes can impact the pharmacokinetics (pharmacogenomics) of the radiopharmaceutical and also the radio-sensitivity (radiogenomics) of cells, it is of great importance to not neglect these emerging fields and adapt their findings to RPT. We propose that to optimize the overall efficacy of RPT, we should account for the genomic phenotypes of each patient which in combination with personalized dosimetry calculations can increase the chances of improving therapeutic outcomes. This is a key component for building the vision of a digital twin for precision nuclear medicine.
Results: The overall impact of the radiogenomics in radiation therapy will be discussed through comprehensive review of the literature. The importance of pharmacogenomics will be demonstrated by summarizing the pharmacokinetic studies. Through the RPT paradigm we will demonstrate the potential impact of these two dimensions of systems biology in efficacy of outcome. Subsequently, the role of radiopharmacogenetics in RPT planning will be discussed.
Conclusions: Genomic constellation of each patient creates a unique biological system that results in distinct response to radiation (radiobiological phenotype) and distinct interaction with injected molecule (pharmacokinetic phenotype). Incorporation of these two phenotypes and their interaction (radiopharmacogenomics) in RPT planning is essential for precision RPT. In this framework, higher tumor control and lower normal tissue toxicities are expected to be obtained.