Challenges in precision medicine in pancreatic cancer: A focus in cancer stem cells and microbiota

Abstract

Pancreatic cancer adenocarcinoma (PDAC) is a lethal disease, with the lowest 5-years survival rate of all cancers due to late diagnosis. Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in PDAC is currently neglectable. The reasons for this dismal situation are mainly the absence of effective early diagnostic biomarkers and therapy resistance. PDAC cancer stem cells (PDAC-SC), which are regarded as essential for tumor initiation, relapse and drug resistance, are highly dependent on their niche i.e. microanatomical structures of the tumor microenvironment. There is an altered microbiome in PDAC patients embedded within the highly desmoplastic tumor microenvironment, which is known to determine therapeutic responses and affecting survival in PDAC patients. We consider that understanding the communication network that exists between the microbiome and the PDAC-SC niche by co-culture of patient-derived organoids (PDOs) with TME microbiota would recapitulate the complexity of PDAC paving the way towards a precision oncology treatment-response prediction.

Keywords: PDAC; cancer stem cell; early diagnosis; microbiota; niche factors; organoid co-culture; precision medicine; therapy resistance.