Targeting signal transduction pathways of cancer stem cells for therapeutic opportunities of metastasis.

Oncotarget

Embryonic and Cancer Stem Cell Research Group, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

Published: November 2016

AI Article Synopsis

  • Tumors consist of a diverse mix of cells, with only specific cancer cells possessing the necessary traits to create secondary tumors; cancer stem cells (CSCs) are critical in this process.
  • The complex relationships and signaling pathways involved in cancer spread, particularly in how CSCs, circulating tumor cells (CTCs), and epithelial-mesenchymal transition (EMT) interact, remain poorly understood but are vital for developing new treatments.
  • Current drug development is focusing on identifying "key driver genes" that support the survival and function of CSCs, aiming to create targeted therapies using various approaches like small molecules and vaccines to combat cancer recurrence and metastasis, which account for about 90% of cancer deaths.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342819PMC
http://dx.doi.org/10.18632/oncotarget.10942DOI Listing

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