Understanding the molecular mechanisms that regulate pancreatic cancer stem cell formation, stemness and chemoresistance: A brief overview

Abstract

Pancreatic cancer is one of the most aggressive cancers worldwide due to the resistances to conventional therapies and early metastasis. Recent research has shown that cancer stem cell populations modulate invasiveness, recurrence, and drug resistance in various cancers, including pancreatic cancer. Pancreatic cancer stem cells (PaCSCs) are characterized by their high plasticity and self-renewal capacities that endow them with unique metabolic, metastatic, and chemoresistant properties. Understanding the exact molecular and signaling mechanisms that underlay malignant processes in PaCSCs is instrumental for developing novel therapeutic modalities that overcome the limitations of current therapeutic regimens. In this paper, we provide an updated review of the latest research in the field and summarize the current knowledge of PaCSCs characteristics, cellular metabolism, stemness, and drug resistance. We explore how the crosstalk between the TME and PaCSCs influences stemness. We also highlight some of the key signalling pathways involved in PaCSCs stemness and drug evasion. The aim of this review is to explore how PaCSCs develop, maintain their properties, and drive tumor relapse in PC. The last section explores some of the latest therapeutic strategies aimed at targeting PaCSCs.