NUT midline carcinoma

US-based Tensha Therapeutics has initiated the first clinical study of TEN-010, a bromodomain and extra-terminal domain (BET) bromodomain inhibitor, for cancer treatment.

This clinical study has been designed to evaluate the safety, tolerability and anti-tumour activity of the TEN-010 in patients with advanced solid tumours that are refractory or intolerant to standard/approved therapies and NUT midline carcinoma (NMC).

NMC is a rare, invariably fatal cancer caused in the majority of cases by a gene translocation event that results in the expression of the NUT protein fused to the BET bromodomains of BRD3 or BRD4.

Tensha chief medical officer Dr Steven Landau said: "We are very pleased to be bringing this new molecule into the clinic in this patient group, for which there is a critical need for new treatment options."

Bromodomain-containing proteins are a class of epigenetic regulators that can influence gene expression once they are bound to chromatin.

Bromodomains play important roles in influencing gene transcription by functioning as readers of epigenetic marks.

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Tensha founder Dr James Bradner has recognised the broad potential of small molecule BET bromodomain inhibitors across a range of therapeutic areas. He has identified NMC as sensitive to BET bromodomain inhibition.

Subsequent studies from Dr Bradner and collaborating laboratories have established BET bromodomain inhibition as a therapeutic strategy to target Myc overexpression and showed the potential of this approach to other cancers that include multiple myeloma, acute myeloid leukemia, non-small cell lung cancer and neuroblastoma.

"Tensha is now poised to test TEN-010’s ability to deliver clinically on the promise that we saw in our preclinical experiments," Dr Bradner said.

Image: Micrograph of a NUT midline carcinoma. Photo: courtesy of Nephron.