Mechanisms of chemotherapy resistance in cervical cancer

Abstract

Cervical cancer (CC) is a leading cause of morbidity and mortality in women globally and in sub-Saharan Africa (SSA), with the human papillomavirus (HPV) being the main cause of CC. Chemotherapy is one of the frontline treatment modalities for this disease. However, chemotherapy resistance is one of the major obstacles that needs to be overcome. This resistance may be due to various cellular and molecular mechanisms. Similar to other cancers, genetic and cellular perturbations in CC are common. These changes may modulate treatment options for patients. Gaining insights into these cellular genetic changes will optimize the best chemotherapy treatment plans, help evade chemotherapy resistance, and improve CC patient outcome. Altered drug transport and metabolism has been reported to be essential in CC drug resistance. Metabolic alterations have been shown to play an important role in the resistance of CC cells to widely used first-line chemotherapeutics. Subclonal cellular populations also play an important role in CC drug resistance. These CC subpopulations may have distinct genetic signatures from progenitor cells, acquiring drug resistance phenotypes. HPV immune evasion mechanisms exploit host factors and promote CC drug resistance. Furthermore, DNA repair pathways, differential methylation patterns, epithelial-to-mesenchymal transition (EMT), and cancer stem cell activation have also been implicated in CC chemoresistance. Thus, this chapter discusses various cellular and molecular mechanisms employed in CC chemoresistance and how combinatorial therapies can aid in overcoming this challenge. Insights into these mechanisms will aid in alleviating treatment resistance burden, improve chemotherapy success, and overall patient outcome.