New paper.
I know that some here have been, or are, on Cabazitaxel. The new study suggest how this "semi-synthetic taxane of the third generation" may be particularly useful against PCa.
Heat Shock Proteins [HSPs] are produced when cells are subjected not just to heat, but also to other existential threats. HSPs are a major cause of radiation resistance. They begin to be produced with the first treatment.
Some HSPs protect by being chaperones. Unfortunately, the Androgen Receptor [AR] is a notable client. The AR becomes a difficult target while under HSP protection.
The study found that Cabazitaxel reduced levels of "HSP90α, HSP40, and HSP70/HSP90", but "did not alter the cytoprotective chemoresistance factor HSP27". "Furthermore, expression of the anti-apoptotic factor HSP60 was suppressed."
"Cabazitaxel additionally inhibits the expression of the AR".
"Thus, cabazitaxel bears an additional anti-proliferative activity which is at least in part specific for PC cells."
-Patrick
ncbi.nlm.nih.gov/pubmed/306...
World J Urol. 2019 Jan 2. doi: 10.1007/s00345-018-2615-x. [Epub ahead of print]
Cabazitaxel inhibits prostate cancer cell growth by inhibition of androgen receptor and heat shock protein expression.
Rottach AM1, Ahrend H1, Martin B1, Walther R2, Zimmermann U1, Burchardt M1, Stope MB3.
Author information
1
Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
2
Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
3
Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany. matthias.stope@uni-greifswald.de.
Abstract
PURPOSE:
Cabazitaxel, a semi-synthetic taxane of the third generation, inhibits prostate cancer (PC) cell growth by affecting the microtubule architecture. Since cabazitaxel has also been demonstrated to inhibit androgen receptor (AR) functionality, AR and AR-associated heat shock protein (HSP) expressions in the presence of cabazitaxel were characterized.
METHODS:
AR and HSP expressions were assessed via Western blotting utilizing a PC-cell-line in vitro system incubated with cabazitaxel.
RESULTS:
Incubation experiments with 0.3 nM cabazitaxel exhibited significantly reduced levels of AR and the AR-associated factors HSP90α, HSP40, and HSP70/HSP90 organising protein. Furthermore, expression of the anti-apoptotic factor HSP60 was suppressed. In contrast to other anticancer compounds, cabazitaxel did not alter the cytoprotective chemoresistance factor HSP27.
CONCLUSIONS:
Despite the deregulation of microtubule organisation, cabazitaxel has been shown to suppress the expression of HSP. Very notably, and may be as a result of down-regulated HSP, cabazitaxel additionally inhibits the expression of the AR in AR-positive PC cells. Thus, cabazitaxel bears an additional anti-proliferative activity which is at least in part specific for PC cells.
KEYWORDS:
Androgen receptor; Cabazitaxel; Chemoresistance; Heat shock proteins; Prostate cancer
PMID: 30603780 DOI: 10.1007/s00345-018-2615-x
