1.TRAIL-coated lipid-nanoparticles overcome resistance to soluble recombinant TRAIL in non-small cell lung cancer cells.
De Miguel D1, Gallego-Lleyda A, Ayuso JM, Erviti-Ardanaz S, Pazo-Cid R, Del Agua C, Fernández LJ, Ochoa I, Anel A, Martinez-Lostao L. Nanotechnology. 2016 May 6;27(18):185101. doi: 10.1088/0957-4484/27/18/185101. Epub 2016 Mar 22.
PURPOSE: Non-small cell lung cancer (NSCLC) is one the types of cancer with higher prevalence and mortality. Apo2-Ligand/TRAIL is a TNF family member able to induce apoptosis in tumor cells but not in normal cells. It has been tested in clinical trials against different types of human cancer including NSCLC. However, results of clinical trials have shown a limited efficacy of TRAIL-based therapies. Recently we have demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) greatly improved TRAIL cytotoxic ability being capable of killing chemoresistant hematological cancer cells. In the present work we have extended the study to NSCLC.
2.Immuno-modulating properties of saliphenylhalamide, SNS-032, obatoclax, and gemcitabine.
Söderholm S1, Anastasina M2, Islam MM2, Tynell J3, Poranen MM4, Bamford DH5, Stenman J6, Julkunen I7, Šaulienė I8, De Brabander JK9, Matikainen S10, Nyman TA11, Saelens X12, Kainov D13. Antiviral Res. 2016 Feb;126:69-80. doi: 10.1016/j.antiviral.2015.12.011. Epub 2015 Dec 29.
Influenza A viruses (IAVs) impact the public health and global economy by causing yearly epidemics and occasional pandemics. Several anti-IAV drugs are available and many are in development. However, the question remains which of these antiviral agents may allow activation of immune responses and protect patients against co- and re-infections. To answer to this question, we analysed immuno-modulating properties of the antivirals saliphenylhalamide (SaliPhe), SNS-032, obatoclax, and gemcitabine, and found that only gemcitabine did not impair immune responses in infected cells. It also allowed activation of innate immune responses in lipopolysaccharide (LPS)- and interferon alpha (IFNα)-stimulated macrophages. Moreover, immuno-mediators produced by gemcitabine-treated IAV-infected macrophages were able to prime immune responses in non-infected cells. Thus, we identified an antiviral agent which might be beneficial for treatment of patients with severe viral infections.
3.Interactions of cyclin-dependent kinase inhibitors AT-7519, flavopiridol and SNS-032 with ABCB1, ABCG2 and ABCC1 transporters and their potential to overcome multidrug resistance in vitro.
Cihalova D1, Staud F, Ceckova M. Cancer Chemother Pharmacol. 2015 Jul;76(1):105-16. doi: 10.1007/s00280-015-2772-1. Epub 2015 May 19.
PURPOSE: ATP-binding cassette (ABC) transporters play an important role in multidrug resistance (MDR) toward anticancer drugs. Here, we evaluated interactions of cyclin-dependent kinase inhibitors (CDKi) AT-7519, flavopiridol and SNS-032 with the following ABC transporters in vitro: P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2) and multidrug resistance-associated protein 1 (ABCC1).
4.Overview of CDK9 as a target in cancer research.
Morales F1, Giordano A1,2. Cell Cycle. 2016 Feb 16;15(4):519-27. doi: 10.1080/15384101.2016.1138186.
CDK9 is a protein in constant development in cancer therapy. Herein we present an overview of the enzyme as a target for cancer therapy. We provide data on its characteristics and mechanism of action. In recent years, CDK9 inhibitors that have been designed with molecular modeling have demonstrated good antitumoral activity in vitro. Clinical studies of the drugs flavopiridol, dinaciclib, seliciclib, SNS-032 and RGB-286638 used as CDK9 inhibitors are also reviewed, with their additional targets and their relative IC50 values. Unfortunately, treatment with these drugs remains unsuccessful and involves many adverse effects. We could conclude that there are many small molecules that bind to CDK9, but their lack of selectivity against other CDKs do not allow them to get to the clinical use. However, drug designers currently have the tools needed to improve the selectivity of CDK9 inhibitors and to make successful treatment available to patients.
