Metastatic Pancreatic Cancer Stem Cell Treatment

Cancer stem cells (CSCs) are believed to be the main drivers of metastasis, chemoresistance, and relapse of pancreatic adenocarcinoma due to their plasticity and cooperation with the tumor microenvironment (Sancho et al. 2016). Due to these diverse functions, complete eradication of CSCs poses a challenge. CSCs are also able to undergo metabolic reprogramming depending on stressors in the tumor microenvironment, and current literature suggests that it is the metabolic plasticity of CSCs themselves that allows for survival in different environmental stressors, leading to further metastasis (Peiris-Pagès et al. 2016). Pancreatic cancer stem cells (PaCSCs) in particular are highly dependent on mitochondrial oxidative phosphorylation (OXPHOS) to survive. This serves as their preferred mechanism for energy production (Sancho et al. 2015). Another hallmark of CSC survival and proliferation is the notion of self-renewal, most commonly driven in PaCSCs through the Notch, Wnt/β-catenin, and Hedgehog signaling pathways (Wong et al. 2019). Therefore, the researchers plan to target PaCSCs through OXPHOS as well as self-renewal signaling in order to most effectively eradicate this metastatic driver.