Targeting Cervical Cancer Stem Cells to Improve Outcomes

 The presence of Cervical Cancer Stem Cells (CCSCs) in cases of Cervical Cancer (CC) represent a small subpopulation of tumor cells with a high potential for resistance to conventional treatments. Therapeutic targeting of CCSCs has the potential to reduce resistance to conventional therapies but also limit the occurrence of distant metastasis and relapse.

Precision medicine researchers working with Sbarro Health Research Organization (SHRO) have published a review which aims to provide an update on CC and CCSCs, including a description of CCSCs’ phenotypes and an outline of the potential of targeting CCSCs in the treatment of CC.

Surgery, chemotherapy (particularly cisplatin), and radiotherapy have improved the overall survival of patients with CC. However, the presence of CCSCs that are resistant to chemo- and radiotherapy leads to disease relapse and a reduction in overall survival. CCSCs can develop resistance to standard treatments via different mechanisms. Owing to their tumorigenicity, CSCs may be the route of cervical carcinogenesis, leading to distant metastasis. Therefore, therapeutic management specifically targeting CSCs is a potential tool for preventing chemo/radio-resistance and decreasing the risk of distant metastasis, tumor relapse, and the generation of secondary tumors, thereby increasing the chances of CC patient survival. The identification of CCSC and a deeper understanding of their microenvironment will enable their specific pharmacological targeting.

The paper, “Cancer Stem Cells and Their Possible Implications in Cervical Cancer: A Short Review,” has been published in the International Journal of Molecular Sciences. Co-authors Riccardo Di Fiore, PhD, and Jean Calleja-Agius, MD, PhD of the University of Malta worked with Antonio Giordano, MD, PhD, Director and Founder of the SHRO and the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia.This paper is based upon work from the COST Action CA18117—European network for Gynaecological Rare Cancer research: From Concept to Cure (GYNOCARE), supported by COST (European Co-operation in Science and Technology). COST is a funding agency for research and innovation networks. All authors are action management committee members and/or form part of the working groups of the GYNOCARE COST Action.

There is currently very limited data available that validate and support the clinical diagnostic value of CCSC biomarkers. The current understanding of these biomarkers suggests that most of them indicate progression of lesions that are already initiated. However, these markers may not be very sensitive to identify all initiated lesions. 

CCSCs also undergo a persistent quiescence state which may contribute to therapy resistance. This is because some of the cytotoxic agents only target cancer cells that are highly proliferating. Once treatment stops, these quiescent CSCs can re-enter the cell cycle and activate cell growth and proliferative signaling pathways, thus accelerating tumor regeneration. The patterns of recurrence and acquired resistance that are observed in post-therapy cancer patients can be explained by the quiescence of CSCs. A deeper understanding of the mechanisms involved, whether activated or silenced, could prove useful for employing combinatorial therapeutic strategies to manipulate and sensitize CSCs to chemotherapy. 

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About the Sbarro Health Research Organization

The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org

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