Background: Radiotherapy outcomes are usually predicted using the Linear Quadratic model. However, this model does not integrate complex features of tumor growth, in particular cell cycle regulation. Methods: In this paper, we propose a multiscale model of cancer growth based on the genetic and molecular features of the evolution of colorectal cancer. The model includes key genes, cellular kinetics, tissue dynamics, macroscopic tumor evolution and radiosensitivity dependence on the cell cycle phase. We investigate the role of gene-dependent cell cycle regulation in the response of tumors to therapeutic irradiation protocols. Results: Simulation results emphasize the importance of tumor tissue features and the need to consider regulating factors such as hypoxia, as well as tumor geometry and tissue dynamics, in predicting and improving radiotherapeutic efficacy. Conclusion: This model provides insight into the coupling of complex biological processes, which leads to a better understanding of oncogenesis. This will hopefully lead to improved irradiation therapy.