Overcoming tumour resistance to treatments with epi-based approaches

Written by Professor Lucia Altucci, Seconda Università degli Studi di Napoli


A main strategy of the drug discovery field is to define novel therapeutic approaches against human disease – including cancer. Clearly, an emerging problem is the potential acquisition of resistance to treatment, even when, a so-called ‘targeted-treatment’ is defined. Very recently, Yujie Tang et al. (Nature Medicine 2014) have suggested a smart, but molecularly well defined, strategy to use epi-based approaches as treatments against a priori treatment-resistant tumours. They indeed discovered that BET bromodomain protein inhibition (see alsoFilippakopoulos P. et aCancercelll., Nature 2010) might turn out beneficial against Hedgehog (Hh)-driven tumours (such as basal cell carcinoma and medulloblastomas) even when resistance to the targeted SMO antagonist-based treatment has been acquired. Even though the idea to use epi-based approaches against cancer for chemo-sensitization has been proposed many times, this example offers a molecular explanation of the potential success of this hypothesis, despite in ‘niche’-type tumours. For the future two main concepts will need to be further developed: real application and toxicity.

Being that BRD-containing complexes are often localised at promoters of key transcription factors, such as c-MYC, BET bromodomain protein inhibition might be effective even in a large cohort of tumours, including in treatment-refractory cancers driven by previously ‘un-targetable’ oncogenes. If proven – and expanded – this hypothesis might modify the treatment and prognosis of refractory tumours in a considerable manner, provided the approach has limited toxicity.

Sam Rose

Journal Development Manager at BioMed Central
Sam studied Biomedical Sciences at the University of Manchester, and is responsible for the development of BioMed Central's genetics journal portfolio.
Sam Rose

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