Despite the continuous recent efforts, cancer remains one of the deadliest diseases worldwide (Bray et al. 2018). Therefore, it is essential to understand the mechanisms of tumor initiation and progression in order to discover new ways to improve cancer therapy. Here, I focused on identifying mechanisms that could potentially contribute to tumor initiation as well as understanding the way of action of chemotherapeutic regimens with the goal to improve their specificity. This thesis is divided into three parts; in the first part, we investigated how defects in the spindle assembly checkpoint (SAC; cellular mechanism that ensures faithful segregation of the genetic material) can contribute to the erroneous segregation of chromosomes in mitosis. In the second part, we focused on how replication stress can impact chromosome segregation and thus chromosomal stability. In the third and last part, we discovered a potential mechanism that cancer cells use to resist treatment.