Overcoming blocks in apoptosis with BH3-mimetic therapy in haematological malignancies

Blocks in apoptosis are now widely regarded as key pathophysiological maladaptations critical for tumour persistence. Importantly, it has also been recognised that they confer resistance to cytotoxic therapy, and hence often portend an adverse prognosis. The advent of BH3-mimetics represents a nascent clinical capability to directly reverse the evasion of apoptosis, and indeed exploit the very molecular abnormalities which have hitherto posed major obstacles to therapeutic success. Clinical trials with BH3-mimetics have demonstrated clear single agent anti-tumour activity in selected haematological malignancies. These drugs also offer promise as adjuncts to existing or emerging therapies in a broader range of cancers.