title: Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy.
abstract: Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Despite an incidence of three cases per million annually, it accounts for an inordinate amount of morbidity and mortality. While the use of chemotherapy (cisplatin, doxorubicin, and methotrexate) in the last century initially resulted in marginal improvement in survival over surgery alone, survival has not improved further in the past four decades. Patients with metastatic osteosarcoma have an especially poor prognosis, with only 30% overall survival. Hence, there is a substantial need for new therapies. The inability to control the metastatic progression of this localized cancer stems from a lack of complete knowledge of the biology of osteosarcoma. Consequently, there has been an aggressive undertaking of scientific investigation of various signaling pathways that could be instrumental in understanding the pathogenesis of osteosarcoma. Here, we review these cancer signaling pathways, including Notch, Wnt, Hedgehog, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT, and JAK/STAT, and their specific role in osteosarcoma. In addition, we highlight numerous natural compounds that have been documented to target these pathways effectively, including curcumin, diallyl trisulfide, resveratrol, apigenin, cyclopamine, and sulforaphane. We elucidate through references that these natural compounds can induce cancer signaling pathway manipulation and possibly facilitate new treatment modalities for osteosarcoma.
authors.affiliation: Division of Hematology and Oncology, Children's Mercy Hospital, Kansas City, MO, 64108, USA.|Department of Surgery, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 3040, Kansas City, KS, 66160, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Angulo
authors.affiliation: Department of Surgery, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 3040, Kansas City, KS, 66160, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaushik
authors.affiliation: Department of Surgery, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 3040, Kansas City, KS, 66160, USA.|The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, 66160, USA.
authors.forename: Dharmalingam
authors.initials: D
authors.lastname: Subramaniam
authors.affiliation: Department of Surgery, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 3040, Kansas City, KS, 66160, USA.
authors.forename: Prasad
authors.initials: P
authors.lastname: Dandawate
authors.affiliation: Division of Hematology and Oncology, Arkansas Children's Hospital, Little Rock, AR, 72202, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Neville
authors.affiliation: Division of Hematology and Oncology, Children's Mercy Hospital, Kansas City, MO, 64108, USA.|Department of Surgery, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 3040, Kansas City, KS, 66160, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Chastain
authors.affiliation: Department of Surgery, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 3040, Kansas City, KS, 66160, USA. sanant@kumc.edu.|The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, 66160, USA. sanant@kumc.edu.
authors.forename: Shrikant
authors.initials: S
authors.lastname: Anant
mesh_terms: D000293:Adolescent; D001688:Biological Products / Q000494:pharmacology*; D002648:Child; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001688:Biological Products
keywords: Ezrin; Natural compounds; Osteosarcoma; Signaling pathways