Abstract
The main aim of oncologists worldwide is to understand and then intervene in the primary tumor initiation and propagation mechanisms. This is essential to allow targeted elimination of cancer cells without altering normal mitotic cells. Currently, there are two main rival theories describing the process of tumorigenesis. According to the Stochastic Model, potentially any cell, once defunct, is capable of initiating carcinogenesis. Alternatively the Cancer Stem Cell (CSC) Model posits that only a small fraction of undifferentiated tumor cells are capable of triggering carcinogenesis. Like healthy stem cells, CSCs are also characterized by a capacity for self-renewal and the ability to generate differentiated progeny, possibly mediating treatment resistance, thus leading to tumor recurrence and metastasis. Moreover, molecular signaling profiles are similar between CSCs and normal stem cells, including Wnt, Notch and Hedgehog pathways. Therefore, development of novel chemotherapeutic agents and proteins (e.g., enzymes and antibodies) specifically targeting CSCs are attractive pharmaceutical candidates. This article describes small molecule inhibitors of stem cell pathways Wnt, Notch and Hedgehog, and their recent chemotherapy clinical trials.
| Original language | English |
|---|---|
| Pages (from-to) | 909-918 |
| Number of pages | 10 |
| Journal | Stem Cell Reviews and Reports |
| Volume | 11 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 1 2015 |
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Keywords
- Cancer
- Hedgehog
- Inhibitor
- Notch
- Signaling pathway
- Stem cells
- Wnt
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
Cite this
Novel Small Molecule Inhibitors of Cancer Stem Cell Signaling Pathways. / Abetov, Danysh; Mustapova, Zhanar; Saliev, Timur; Bulanin, Denis; Batyrbekov, Kanat; Gilman, Charles P.
In: Stem Cell Reviews and Reports, Vol. 11, No. 6, 01.12.2015, p. 909-918.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel Small Molecule Inhibitors of Cancer Stem Cell Signaling Pathways
AU - Abetov, Danysh
AU - Mustapova, Zhanar
AU - Saliev, Timur
AU - Bulanin, Denis
AU - Batyrbekov, Kanat
AU - Gilman, Charles P.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - The main aim of oncologists worldwide is to understand and then intervene in the primary tumor initiation and propagation mechanisms. This is essential to allow targeted elimination of cancer cells without altering normal mitotic cells. Currently, there are two main rival theories describing the process of tumorigenesis. According to the Stochastic Model, potentially any cell, once defunct, is capable of initiating carcinogenesis. Alternatively the Cancer Stem Cell (CSC) Model posits that only a small fraction of undifferentiated tumor cells are capable of triggering carcinogenesis. Like healthy stem cells, CSCs are also characterized by a capacity for self-renewal and the ability to generate differentiated progeny, possibly mediating treatment resistance, thus leading to tumor recurrence and metastasis. Moreover, molecular signaling profiles are similar between CSCs and normal stem cells, including Wnt, Notch and Hedgehog pathways. Therefore, development of novel chemotherapeutic agents and proteins (e.g., enzymes and antibodies) specifically targeting CSCs are attractive pharmaceutical candidates. This article describes small molecule inhibitors of stem cell pathways Wnt, Notch and Hedgehog, and their recent chemotherapy clinical trials.
AB - The main aim of oncologists worldwide is to understand and then intervene in the primary tumor initiation and propagation mechanisms. This is essential to allow targeted elimination of cancer cells without altering normal mitotic cells. Currently, there are two main rival theories describing the process of tumorigenesis. According to the Stochastic Model, potentially any cell, once defunct, is capable of initiating carcinogenesis. Alternatively the Cancer Stem Cell (CSC) Model posits that only a small fraction of undifferentiated tumor cells are capable of triggering carcinogenesis. Like healthy stem cells, CSCs are also characterized by a capacity for self-renewal and the ability to generate differentiated progeny, possibly mediating treatment resistance, thus leading to tumor recurrence and metastasis. Moreover, molecular signaling profiles are similar between CSCs and normal stem cells, including Wnt, Notch and Hedgehog pathways. Therefore, development of novel chemotherapeutic agents and proteins (e.g., enzymes and antibodies) specifically targeting CSCs are attractive pharmaceutical candidates. This article describes small molecule inhibitors of stem cell pathways Wnt, Notch and Hedgehog, and their recent chemotherapy clinical trials.
KW - Cancer
KW - Hedgehog
KW - Inhibitor
KW - Notch
KW - Signaling pathway
KW - Stem cells
KW - Wnt
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UR - http://www.scopus.com/inward/citedby.url?scp=84947612337&partnerID=8YFLogxK
U2 - 10.1007/s12015-015-9612-x
DO - 10.1007/s12015-015-9612-x
M3 - Article
C2 - 26210995
AN - SCOPUS:84947612337
VL - 11
SP - 909
EP - 918
JO - Stem Cell Reviews
JF - Stem Cell Reviews
SN - 1550-8943
IS - 6
ER -