Targeting Cervical Cancer Stem Cells to Improve Outcomes
The presence of cervical cancer stem cells (CCSCs) in cases of cervical cancer represents 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.
Researchers from the Faculty of Medicine and Surgery at the University of Malta have collaborated with Prof Antonio Giordano from the Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia; Prof Francesca Pentimalli Department of Medicine and Surgery, LUM University “Giuseppe DeGennaro”, 70010 Casamassima, Italy; and Dr Yashwanth Subbannayya from the Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway in order to investigate the possible implications of cancer stem cells in cervical cancer.
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 survival for patients with cervical cancer. 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. This review 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 cervical cancer.
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.