Novel agents and future directions for refractory breast cancer.

Tumor resistance remains a major clinical challenge. Numerous pathways are under investigation to determine how best to target therapies to specific mutations in tumor biology and circumvent resistance. Agents in development include inhibitors of the poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) pathway, such as iniparib, olaparib, and veliparib; the PI3K/Akt/mTOR pathway inhibitor everolimus; and the Src family tyrosine kinase inhibitor dasatinib. Research is ongoing to determine whether patients with specific biochemical attributes, such as the presence of a BRCA1 or BRCA2 mutation, will have a better response to targeted therapy and whether targeted agents act synergistically with chemotherapeutic agents.