Cathepsins, chemoresistance, and cancer

Cancer chemoresistance poses a significant challenge in the effective treatment of various malignancies, limiting the success of chemotherapy regimens and contributing to disease recurrence. Cathepsins, a family of lysosomal proteases, have emerged as key players in the intricate network of molecular events that underlie chemoresistance in cancer cells. This chapter aims to provide a comprehensive overview of the current understanding of the involvement of cathepsins in the development and maintenance of chemoresistance. The intricate mechanisms through which cathepsins contribute to chemoresistance include their participation in cellular processes such as autophagy, apoptosis evasion, and drug metabolism. Moreover, cathepsins can modulate the tumor microenvironment, influencing factors such as angiogenesis and immune response, further impacting the response to chemotherapy. Dysregulation of cathepsin expression and activity has been observed in various cancer types, and their prognostic significance highlights their potential as biomarkers for predicting chemotherapeutic outcomes. Recent advances in the development of cathepsin-targeted therapies are also discussed, emphasizing the potential of cathepsin inhibitors as adjuvants to conventional chemotherapy. Strategies to selectively target cathepsins and overcome chemoresistance are explored, including the development of small-molecule inhibitors, antibody-based therapies, and nanoparticle delivery systems. In conclusion, understanding the complicated involvement of cathepsins in cancer chemoresistance provides valuable insights into the development of novel therapeutic strategies. Targeting cathepsins may represent a promising approach to enhance the efficacy of chemotherapy and improve patient outcomes in the battle against resistant malignancies. Further research is warranted to elucidate the specific roles of individual cathepsin family members in different cancer types and to optimize the clinical translation of cathepsin-targeted therapies.