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

Waqas Iqbal, Saleh Alkarim, Ahmed AlHejin, Hasan Mukhtar _ and Kulvinder S. Saini

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Oncotarget. 2016; 7:76337-76353. https://doi.org/10.18632/oncotarget.10942

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Waqas Iqbal1, Saleh Alkarim1, Ahmed AlHejin1, Hasan Mukhtar1,2 and Kulvinder S. Saini1,3

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

2 Department of Dermatology, University of Wisconsin Medical Sciences Center, Madison, WI, USA

3 School of Biotechnology, Eternal University, Baru Sahib, Himachal Pradesh, India

Correspondence to:

Hasan Mukhtar, email:

Kulvinder Saini, email:

Keywords: stem cells, cancer, metastasis, therapeutic, signaling

Received: May 16, 2016 Accepted: July 13, 2016 Published: July 29, 2016


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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