Abstract
The ability to evade apoptosis is one of the defining hallmarks of cancer. It enables the survival of cancer cells under abnormal growth stimulation and mediates their increased resistance to treatment with cytotoxic drugs and radiation. Therefore, antiapoptotic proteins that counteract apoptosis signaling represent promising new therapeutic targets to impair cancer cell growth and enhance treatment response. As soon as RNA interference (RNAi) was demonstrated in mammalian cells, it rapidly became an essential tool for gene knockdown in preclinical models, making it possible to define the role of specific genes in the onset and progression of cancer and explore their potential as therapeutic targets. The present review summarizes the findings from studies relying on the use of RNAi-based approaches to functionally validate two members of the inhibitors of apoptosis protein family, survivin and Apollon/BRUCE, as new cancer therapeutic targets. Results collected thus far indicate that targeting the survivin network efficiently inhibits tumor growth potential and increases spontaneous and treatment-induced apoptosis of cancer cells. Based on these findings, the applicability of survivin-directed strategies for the clinical treatment of human tumors is currently under investigation. As regards Apollon/ BRUCE, although very preliminary, results of RNAi-mediated gene knockdown point to the possibility to significantly impair tumor cell proliferation through the induction of apoptosis.
| Original language | English |
|---|---|
| Pages (from-to) | 69-78 |
| Number of pages | 10 |
| Journal | Current Topics in Medicinal Chemistry |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 2012 |
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Keywords
- Apollon/BRUCE
- Apoptosis
- Chemosensitivity
- Human tumors
- Inhibitors of apoptosis proteins
- Radiosensitivity
- Survivin
ASJC Scopus subject areas
- Drug Discovery
Cite this
RNA interference-mediated validation of survivin and Apollon/BRUCE as new therapeutic targets for cancer therapy. / Pennati, Marzia; Millo, Enrico; Gandellini, Paolo; Folini, Marco; Zaffaroni, Nadia.
In: Current Topics in Medicinal Chemistry, Vol. 12, No. 2, 01.2012, p. 69-78.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - RNA interference-mediated validation of survivin and Apollon/BRUCE as new therapeutic targets for cancer therapy
AU - Pennati, Marzia
AU - Millo, Enrico
AU - Gandellini, Paolo
AU - Folini, Marco
AU - Zaffaroni, Nadia
PY - 2012/1
Y1 - 2012/1
N2 - The ability to evade apoptosis is one of the defining hallmarks of cancer. It enables the survival of cancer cells under abnormal growth stimulation and mediates their increased resistance to treatment with cytotoxic drugs and radiation. Therefore, antiapoptotic proteins that counteract apoptosis signaling represent promising new therapeutic targets to impair cancer cell growth and enhance treatment response. As soon as RNA interference (RNAi) was demonstrated in mammalian cells, it rapidly became an essential tool for gene knockdown in preclinical models, making it possible to define the role of specific genes in the onset and progression of cancer and explore their potential as therapeutic targets. The present review summarizes the findings from studies relying on the use of RNAi-based approaches to functionally validate two members of the inhibitors of apoptosis protein family, survivin and Apollon/BRUCE, as new cancer therapeutic targets. Results collected thus far indicate that targeting the survivin network efficiently inhibits tumor growth potential and increases spontaneous and treatment-induced apoptosis of cancer cells. Based on these findings, the applicability of survivin-directed strategies for the clinical treatment of human tumors is currently under investigation. As regards Apollon/ BRUCE, although very preliminary, results of RNAi-mediated gene knockdown point to the possibility to significantly impair tumor cell proliferation through the induction of apoptosis.
AB - The ability to evade apoptosis is one of the defining hallmarks of cancer. It enables the survival of cancer cells under abnormal growth stimulation and mediates their increased resistance to treatment with cytotoxic drugs and radiation. Therefore, antiapoptotic proteins that counteract apoptosis signaling represent promising new therapeutic targets to impair cancer cell growth and enhance treatment response. As soon as RNA interference (RNAi) was demonstrated in mammalian cells, it rapidly became an essential tool for gene knockdown in preclinical models, making it possible to define the role of specific genes in the onset and progression of cancer and explore their potential as therapeutic targets. The present review summarizes the findings from studies relying on the use of RNAi-based approaches to functionally validate two members of the inhibitors of apoptosis protein family, survivin and Apollon/BRUCE, as new cancer therapeutic targets. Results collected thus far indicate that targeting the survivin network efficiently inhibits tumor growth potential and increases spontaneous and treatment-induced apoptosis of cancer cells. Based on these findings, the applicability of survivin-directed strategies for the clinical treatment of human tumors is currently under investigation. As regards Apollon/ BRUCE, although very preliminary, results of RNAi-mediated gene knockdown point to the possibility to significantly impair tumor cell proliferation through the induction of apoptosis.
KW - Apollon/BRUCE
KW - Apoptosis
KW - Chemosensitivity
KW - Human tumors
KW - Inhibitors of apoptosis proteins
KW - Radiosensitivity
KW - Survivin
UR - http://www.scopus.com/inward/record.url?scp=84855841415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855841415&partnerID=8YFLogxK
U2 - 10.2174/156802612798919169
DO - 10.2174/156802612798919169
M3 - Article
C2 - 22196277
AN - SCOPUS:84855841415
VL - 12
SP - 69
EP - 78
JO - Current Topics in Medicinal Chemistry
JF - Current Topics in Medicinal Chemistry
SN - 1568-0266
IS - 2
ER -