Methods of treating cancer using antisense based therapies including antisense oligonucleotides of si RNAs directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense based therapies can be used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.