title: Novel Small Molecule Inhibitors of Cancer Stem Cell Signaling Pathways.
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.
authors.affiliation: Laboratory of Translational Medicine and Life Sciences Technologies, Centre for Life Sciences, Nazarbayev University, Unit 9, 53 Kabanbay batyr Ave., Astana, 010000, Kazakhstan.
authors.forename: Danysh
authors.initials: D
authors.lastname: Abetov
authors.affiliation: Laboratory of Translational Medicine and Life Sciences Technologies, Centre for Life Sciences, Nazarbayev University, Unit 9, 53 Kabanbay batyr Ave., Astana, 010000, Kazakhstan.
authors.forename: Zhanar
authors.initials: Z
authors.lastname: Mustapova
authors.affiliation: Laboratory of Translational Medicine and Life Sciences Technologies, Centre for Life Sciences, Nazarbayev University, Unit 9, 53 Kabanbay batyr Ave., Astana, 010000, Kazakhstan. tim.saliev@gmail.com.
authors.forename: Timur
authors.initials: T
authors.lastname: Saliev
authors.affiliation: School of Medicine, Nazarbayev University, Unit 9, 53 Kabanbay batyr Ave., Astana, 010000, Kazakhstan.
authors.forename: Denis
authors.initials: D
authors.lastname: Bulanin
authors.affiliation: Research Institute of Traumatology and Orthopedics, Astana, 010000, Kazakhstan.
authors.forename: Kanat
authors.initials: K
authors.lastname: Batyrbekov
authors.affiliation: School of Science and Technology, Nazarbayev University, Unit 7, 53 Kabanbay batyr Ave., Astana, 010000, Kazakhstan.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Gilman
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D051880:Receptors, Notch / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins
keywords: Cancer; Hedgehog; Inhibitor; Notch; Signaling pathway; Stem cells; Wnt