Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reduction of resistance to the treatment, prevention, and/or diagnosis of diseases characterized by the formation of cancers. Embodiments include methods of treating cancer, comprising the steps of: providing a patient diagnosed with cancer with a therapeutic regime that includes at least one therapeutically effective dose of at least one agent that reduces the activity of at least one DNA damage/repair pathway. Other embodiments include methods of treating cancer, comprising the steps of: treating a patient diagnosed with cancer with a combination of therapeutic agents that includes at least one therapeutically effective anti-cancer agent and at least one compound that reduces the activity of at least one DNA damage/repair pathway. Yet other embodiments include methods of reducing resistance to a genotoxic therapeutic, comprising the steps of: treating a patient at least one therapeutically effective dose of at least one agent that reduces at least one DNA damage/repair pathway.