The roles of intratumour heterogeneity in the biology and treatment of pancreatic ductal adenocarcinoma

• Published in: Oncogene Vol. 41; no. 42; pp. 4686 - 4695
• Main Authors: Evan, Theodore, Wang, Victoria Min-Yi, Behrens, Axel
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 14.10.2022; Nature Publishing Group UK
• Subjects: Adenocarcinoma; Biology; Cancer research; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - therapy; Epigenetics; Histology; Humans; Laboratories; Lung cancer; Medical research; Metabolism; Metastases; Microenvironments; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - therapy; Phenotypes; Review; Stem cells; Stromal cells; Surgery; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-022-02448-x

Intratumour heterogeneity (ITH) has become an important focus of cancer research in recent years. ITH describes the cellular variation that enables tumour evolution, including tumour progression, metastasis and resistance to treatment. The selection and expansion of genetically distinct treatment-resistant cancer cell clones provides one explanation for treatment failure. However, tumour cell variation need not be genetically encoded. In pancreatic ductal adenocarcinoma (PDAC) in particular, the complex tumour microenvironment as well as crosstalk between tumour and stromal cells result in exceptionally variable tumour cell phenotypes that are also highly adaptable. In this review we discuss four different types of phenotypic heterogeneity within PDAC, from morphological to metabolic heterogeneity. We suggest that these different types of ITH are not independent, but, rather, can inform one another. Lastly, we highlight recent findings that suggest how therapeutic efforts may halt PDAC progression by constraining cellular heterogeneity.