Interfering with gene expression to fight cancer

Immag of a NUT midline carcinoma, a tumour caused by the alteration of a BET protein (source: Wikipedia)
Immag of a NUT midline carcinoma, a tumour caused by the alteration of a BET protein (source: Wikipedia)
Simplified diagram of the BET inhibitors mechanism
Simplified diagram of the BET inhibitors mechanism

Institutional Communication Service

12 January 2018

Cancer Discovery, AACR (American Association for Cancer Research) top journal, has invited Anastasios Stathis of the Oncology Institute of Southern Switzerland (IOSI), and Francesco Bertoni of the Institute of Oncology Research (IOR, Affiliated with USI) to review the laboratory and clinical development of a new class of cancer drugs.  

Each cell, including tumour cells, knows at the right time, which genes to expresses, thanks to a complex system of regulation involving a number of molecules. BET proteins tell other molecules which genes to expressed and transform into proteins. BET inhibitors are a class of newly developed drugs that cut the link between the DNA and BET proteins. Laboratory tests have shown the effectiveness of such inhibitors on different tumours, since the most important genes for neoplastic cells are among the genes controlled by BET proteins. The research group led by Francesco Bertoni (group leader and vice director of IOR; vice president of SAKK (Swiss Group for Clinical Cancer Research) group lymphoma, and active member of SAKK group for new drugs) has worked extensively with BET inhibitors, especially with one called OTX015, on lymphomas models, but also on solid tumours such as lung and breast cancer. Anastasios Stathis (New Drugs Unit manager and Head of Clinical Research at IOSI; vice president of SAKK group for new drugs, and active member of the SAKK group lymphoma) was among the first researchers to treat lymphoma or NUT carcinoma patients, the latter being a rare cancer characterised by a genetic lesion that activates BET proteins. 

 

In the article recently published on Cancer Discovery, Stathis and Bertoni illustrate the current results of these drugs, using data acquired both in laboratory tests and in clinical trials. While in laboratory BET inhibitors have a very extensive anti-tumour activity, the first clinical data show a positive outcome in a limited number of patients. It will be critical to see results from the use of BET inhibitors in subgroups of genetically well-characterised patients, combined with other drugs as suggested by laboratory data, and with the introduction of next- generation molecules. 

 

For publication references: http://cancerdiscovery.aacrjournals.org/content/8/1/24

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