Smac-mimetic combination therapies for the treatment of cancer and infectious disease

Abstract

Acute myeloid leukaemia (AML) is an aggressive disease with a current 5-year survival rate of only ~30%, therefore development of more effective treatments is urgently needed. Overexpression of inhibitor of apoptosis (IAP) proteins, responsible for the regulation of tumour necrosis factor (TNF)-mediated apoptosis, have been correlated with cancer progression and treatment resistance. Natural IAP antagonists exist, termed second mitochondria-derived activator of caspases or Smac, leading to the pharmaceutical development of Smac-mimetics. Smac-mimetics, such as the drug birinapant, are currently in clinical trials for a range of cancers, including AML. Although, birinapant has shown promising..