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Br J Haematol. 2015 Nov;171(3):378-86. doi: 10.1111/bjh.13595. Epub 2015 Aug 3.

The novel atypical retinoid ST5589 down-regulates Aurora Kinase A and has anti-tumour activity in lymphoma pre-clinical models.

Author information

1
Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
2
Dalle Molle Institute for Artificial Intelligence (IDSIA), Manno, Switzerland.
3
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
4
IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
5
Research & Development, Sigma-Tau, Pomezia, Italy.

Abstract

Despite the marked improvements in the treatment of lymphomas, there is still a need for new therapeutic agents. Synthetic retinoids represent a class of compounds with anti-cancer activity. Here, we report the preclinical activity of a new member of this class, the ST1926-derivative ST5589, in lymphomas. ST5589 presented a dose-dependent anti-proliferative activity in almost all of the 25 lymphoma cell lines analysed, with a median 50% inhibitory concentration of 433 nM. Apoptosis was observed in 8/11 cell lines. ST5589 induced changes in the gene expression profiles of the cell lines, including the down-regulation of Aurora Kinase A (AURKA). Specific gene expression signatures were associated with a higher sensitivity to the compound and combination of ST5589 with carfilzomib revealed the importance of proteasome activity in mediating the anti-tumour activity of ST5589. In conclusion, we have identified a new mechanism of action of atypical retinoids as anti-cancer compounds, and the encouraging results obtained with the new ST1926-derivative ST5589 provide the basis for further developments of the compound.

KEYWORDS:

MYC; ST1926; aurora kinase; lymphomas; new drugs for lymphoma; retinoids

PMID:
26235926
DOI:
10.1111/bjh.13595
[Indexed for MEDLINE]

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