Targeting Fibrosis in Pancreatic Ductal Adenocarcinoma: Emerging Role of Endothelial-to-Mesenchymal Transition

Despite advances in our understanding of tumour biology and rapid strides in cancer therapies, malignant tumours remain a leading cause of morbidity and mortality [1-3]. Among these tumours, pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of mortality worldwide, with the lowest five-year survival rate [4-6]. Therefore, development of novel therapeutic strategies remains the urgent need of the hour. Poorly vascularized tumours like PDAC have remained largely untreatable despite the substantial innovations in anti-angiogenesis therapies [7,8]. At the morphological level, PDAC is characterized by an intense fibrotic reaction called tumour desmoplasia, primarily composed of the cancer-associated fibroblasts (CAFs) along with other stromal cells [9-12]. Recent findings have highlighted the crucial role of CAFs in numerous oncogenic events through alteration of the tumour microenvironment by releasing oncogenic as well as angiogenic factors [13-15]. Highly fibrotic PDAC tumours are often resistant to chemotherapy and radiation therapy due to high interstitial pressure and tumour microenvironment. This raised the question, “Could evolution of anti-fibrosis therapies treat PDAC?”