| Title |
Clusterin: a key player in cancer chemoresistance and its inhibition
|
|---|---|
| Published in |
OncoTargets and therapy, March 2014
|
| DOI | 10.2147/ott.s58622 |
| Pubmed ID | |
| Authors |
Tomas Koltai |
| Abstract |
Clusterin is a heterodimeric disulfide-linked glycoprotein (449 amino acids) isolated in the rat prostate after castration. It is widely distributed in different tissues and highly conserved in species. There are two isoforms (1 and 2) with antagonistic actions regarding apoptosis. Clusterin is implicated in a number of biological processes, including lipid transport, membrane recycling, cell adhesion, programmed cell death, and complement cascade, representing a truly multifunctional protein. Isoform 2 is overexpressed under cellular stress conditions and protects cells from apoptosis by impeding Bax actions on the mitochondrial membrane and exerts other protumor activities, like phosphatidylinositol 3-kinase/protein kinase B pathway activation, modulation of extracellular signal-regulated kinase 1/2 signaling and matrix metallopeptidase-9 expression, increased angiogenesis, modulation of the nuclear factor kappa B pathway, among others. Its overexpression should be considered as a nonspecific cellular response to a wide variety of tissue insults like cytotoxic chemotherapy, radiation, excess of free oxygen radicals, androgen or estrogen deprivation, etc. A review of the recent literature strongly suggests potential roles for custirsen in particular, and proapoptosis treatments in general, as novel modalities in cancer management. Inhibition of clusterin is known to increase the cytotoxic effects of chemotherapeutic agents, and custirsen, a second-generation antisense oligonucleotide that blocks clusterin, is being tested in a Phase III clinical trial after successful results were achieved in Phase II studies. A major issue in cancer evolution that remains unanswered is whether clusterin represents a driving force of tumorigenesis or a late phenomenon after chemotherapy. This review presents preclinical data that encourages trials in various types of cancer other than advanced castration-resistance prostate cancer and discusses briefly the appropriate timing for clusterin inhibition in the clinical context. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Central African Republic | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 147 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 2 | 1% |
| Sweden | 1 | <1% |
| Czechia | 1 | <1% |
| Thailand | 1 | <1% |
| Unknown | 142 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 24 | 16% |
| Researcher | 21 | 14% |
| Student > Master | 20 | 14% |
| Student > Bachelor | 18 | 12% |
| Student > Postgraduate | 9 | 6% |
| Other | 22 | 15% |
| Unknown | 33 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 34 | 23% |
| Biochemistry, Genetics and Molecular Biology | 25 | 17% |
| Medicine and Dentistry | 19 | 13% |
| Neuroscience | 12 | 8% |
| Immunology and Microbiology | 5 | 3% |
| Other | 15 | 10% |
| Unknown | 37 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 July 2023.
All research outputs
#7,430,186
of 25,584,565 outputs
Outputs from OncoTargets and therapy
#379
of 2,967 outputs
Outputs of similar age
#66,354
of 236,752 outputs
Outputs of similar age from OncoTargets and therapy
#3
of 17 outputs
Altmetric has tracked 25,584,565 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 2,967 research outputs from this source. They receive a mean Attention Score of 3.0. This one has done well, scoring higher than 85% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 236,752 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.