Proteasome inhibitors
Proteasome inhibitors suppress the growth of some tumors. Currently, bortezomib is used clinically for the treatment of multiple myeloma, or mantle cell lymphoma. The effect on other tumors is being tested.
– Further reading: Proteasome inhibitors / history
Although there have already been hundreds of studies devoted to the effects of bortezomib on the whole organism and on cell cultures, we still do not know why this drug preferentially kills cancer cells and allows healthy cells to live. What is certain is that proteasome inhibition represents a simultaneous intervention in a huge number of cellular events at once. In different tumor cell lines, this drug induces different changes in vitro.
– Further reading: Proteasome inhibitors / studies
Disadvantages of the therapy[edit | edit source]
Unfortunately, bortezomib has some drawbacks: it is given by injection and is not very effective against many types of tumors. It generally does not work against solid tumors. Even multiple myeloma cells usually develop resistance to it over time. There is therefore an obvious demand for additional proteasome inhibitors that could bring more benefits to oncology patients and new profits to pharmaceutical companies. Second-generation 20S proteasome inhibitors are currently being developed.
– Further reading: Proteasome inhibitors / second generation
Antabuse / Disulfiram[edit | edit source]
So far, an exotic possibility to influence the ubiquitin-proteasome system is the inhibition of deubiquitinases. In 2007, Poh1 was proposed as one of the promising targets of antitumor therapy. It is a deubiquitinase that cleaves a polyubiquitin chain from a protein bound to the 26S proteasome[1].
The use of a drug that has been used for decades in the treatment of alcoholism is being considered. Antabus® (disulfiram) can inhibit Poh1 and other JAMM domain DUBs. An overview of the entire issue can be found in the publication [2]. The actual inhibitor is most likely dithiocarb, a metabolite of disulfiram, in a complex with copper.
– Further reading: Proteasome inhibitors / disulfiram (Antabuse)
References[edit | edit source]
Related articles[edit | edit source]
- Proteins
- Degradation of proteins
- Ubiquitination
- Deubiquitination
- Ubiquitin-proteasome system / history
- Proteasome
- Translation
Bibliography[edit | edit source]
- CVEK, Boris. Od ubikvitinu k antabusu. Britské listy : deník o všem, o čem se v České republice příliš nemluví [online]. 2011, vol. -, p. -, Available from <https://blisty.cz//legacy.blisty.cz/art/56680.html>. ISSN 1213-1792.
References[edit | edit source]
- ↑ GALLERY, Melissa – BLANK, Jonathan L – LIN, Yinghui. , et al. The JAMM motif of human deubiquitinase Poh1 is essential for cell viability. Mol Cancer Ther [online]. 2007, vol. 1, p. 262-8, Available from <https://www.ncbi.nlm.nih.gov/pubmed/17237285>. ISSN 1535-7163.
- ↑ CVEK, Boris. Targeting Malignancies with Disulfiram (Antabuse): Multidrug Resistance, Angiogenesis, and Proteasome. Curr Cancer Drug Targets [online]. 2011, vol. 11, p. 332-337(6), Available from <https://www.ncbi.nlm.nih.gov/pubmed/21247389>. ISSN 1568-0096 (print), 1873-5576.
Proteasome inhibitors suppress the growth of some tumors. Currently, bortezomib is used clinically for the treatment of multiple myeloma
, or
mantle cell lymphoma
. The effect on other tumors is being tested.
– Further reading: Proteasome inhibitors / history
Although there have already been hundreds of studies devoted to the effects of bortezomib on the whole organism and on cell cultures, we still do not know why this drug preferentially kills cancer cells and allows healthy cells to live. What is certain is that proteasome inhibition represents a simultaneous intervention in a huge number of cellular events at once. In different tumor cell lines, this drug induces different changes in vitro.
– Further reading: Proteasome inhibitors / studies
Disadvantages of the therapy
Unfortunately, bortezomib has some drawbacks: it is given by injection and is not very effective against many types of tumors. It generally does not work against solid tumors. Even multiple myeloma
cells usually develop resistance to it over time. There is therefore an obvious demand for additional proteasome inhibitors that could bring more benefits to oncology patients and new profits to pharmaceutical companies.
Second-generation 20S proteasome inhibitors
are currently being developed.
– Further reading: Proteasome inhibitors / second generation
Antabuse / Disulfiram
So far, an exotic possibility to influence the ubiquitin-proteasome system
is the inhibition of deubiquitinases. In 2007, Poh1 was proposed as one of the promising targets of antitumor therapy. It is a deubiquitinase that cleaves a polyubiquitin chain from a protein bound to the 26S proteasome[1].
The use of a drug that has been used for decades in the treatment of alcoholism is being considered. Antabus® (disulfiram) can inhibit Poh1 and other JAMM domain DUBs. An overview of the entire issue can be found in the publication [2]. The actual inhibitor is most likely dithiocarb, a metabolite of disulfiram, in a complex with copper
.
Disulfiram (Antabuse) structure
– Further reading: Proteasome inhibitors / disulfiram (Antabuse)
References
Related articles
Bibliography
- CVEK, Boris. Od ubikvitinu k antabusu. Britské listy : deník o všem, o čem se v České republice příliš nemluví [online]. 2011, vol. -, p. -, Available from <https://blisty.cz//legacy.blisty.cz/art/56680.html>. ISSN 1213-1792.
References
- ↑ GALLERY, Melissa – BLANK, Jonathan L – LIN, Yinghui. , et al. The JAMM motif of human deubiquitinase Poh1 is essential for cell viability. Mol Cancer Ther [online]. 2007, vol. 1, p. 262-8, Available from <https://www.ncbi.nlm.nih.gov/pubmed/17237285>. ISSN 1535-7163.
- ↑ CVEK, Boris. Targeting Malignancies with Disulfiram (Antabuse): Multidrug Resistance, Angiogenesis, and Proteasome. Curr Cancer Drug Targets [online]. 2011, vol. 11, p. 332-337(6), Available from <https://www.ncbi.nlm.nih.gov/pubmed/21247389>. ISSN 1568-0096 (print), 1873-5576.
