Table 1.

Barriers to effective molecularly targeted therapy in pancreatic ductal adenocarcinoma

PDAC biology	Barrier
Genetic heterogeneity	Inability to directly inhibit KRAS
	Convergence of signal transduction pathways downstream from KRAS with feedback inhibitory loops
Overexpression of EGFR, IGF-1R	Escape from growth factor dependence in later stages of tumorigenesis
Desmoplastic stroma	Hypoxic tumor milieu impairs effective drug delivery
Overexpression of angiogenic factors	Secretion of angiostatic factors in tumor microenvironment
PDAC stem cells	Difficult to eradicate subpopulation of cells capable of self-renewal Resistance to chemotherapy, radiation
Low immunogenicity	Evasion of host immunity Abundance of immunosuppressive cells in tumor milieu

PDAC: Pancreatic ductal adenocarcinoma; KRAS: Kirsten rat sarcoma oncogene; EGFR: Epidermal growth factor receptor; IGF-1R: Insulin like growth factor-1 receptor.