title: Targeting signal transduction pathways of cancer stem cells for therapeutic opportunities of metastasis.
abstract: Tumor comprises of heterogeneous population of cells where not all the disseminated cancer cells have the prerogative and "in-build genetic cues" to form secondary tumors. Cells with stem like properties complemented by key signaling molecules clearly have shown to exhibit selective growth advantage to form tumors at distant metastatic sites. Thus, defining the role of cancer stem cells (CSC) in tumorigenesis and metastasis is emerging as a major thrust area for therapeutic intervention. Precise relationship and regulatory mechanisms operating in various signal transduction pathways during cancer dissemination, extravasation and angiogenesis still remain largely enigmatic. How the crosstalk amongst circulating tumor cells (CTC), epithelial mesenchymal transition (EMT) process and CSC is coordinated for initiating the metastasis at secondary tissues, and during cancer relapse could be of great therapeutic interest. The signal transduction mechanisms facilitating the dissemination, infiltration of CSC into blood stream, extravasations, progression of metastasis phenotype and angiogenesis, at distant organs, are the key pathologically important vulnerabilities being elucidated. Therefore, current new drug discovery focus has shifted towards finding "key driver genes" operating in parallel signaling pathways, during quiescence, survival and maintenance of stemness in CSC. Understanding these mechanisms could open new horizons for tackling the issue of cancer recurrence and metastasis-the cause of ~90% cancer associated mortality. To design futuristic & targeted therapies, we propose a multi-pronged strategy involving small molecules, RNA interference, vaccines, antibodies and other biotechnological modalities against CSC and the metastatic signal transduction cascade.
authors.affiliation: Embryonic and Cancer Stem Cell Research Group, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Waqas
authors.initials: W
authors.lastname: Iqbal
authors.affiliation: Embryonic and Cancer Stem Cell Research Group, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Alkarim
authors.affiliation: Embryonic and Cancer Stem Cell Research Group, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: AlHejin
authors.affiliation: Embryonic and Cancer Stem Cell Research Group, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.|Department of Dermatology, University of Wisconsin Medical Sciences Center, Madison, WI, USA.
authors.forename: Hasan
authors.initials: H
authors.lastname: Mukhtar
authors.affiliation: Embryonic and Cancer Stem Cell Research Group, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.|School of Biotechnology, Eternal University, Baru Sahib, Himachal Pradesh, India.
authors.forename: Kulvinder S
authors.initials: KS
authors.lastname: Saini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents
keywords: cancer; metastasis; signaling; stem cells; therapeutic