Copyright ©The Author(s) 2016.
World J Gastrointest Oncol. Apr 15, 2016; 8(4): 366-379
Published online Apr 15, 2016. doi: 10.4251/wjgo.v8.i4.366
Table 1 Barriers to effective molecularly targeted therapy in pancreatic ductal adenocarcinoma
PDAC biologyBarrier
Genetic heterogeneityInability to directly inhibit KRAS
Convergence of signal transduction pathways downstream from KRAS with feedback inhibitory loops
Overexpression of EGFR, IGF-1REscape from growth factor dependence in later stages of tumorigenesis
Desmoplastic stromaHypoxic tumor milieu impairs effective drug delivery
Overexpression of angiogenic factorsSecretion of angiostatic factors in tumor microenvironment
PDAC stem cellsDifficult to eradicate subpopulation of cells capable of self-renewal Resistance to chemotherapy, radiation
Low immunogenicityEvasion of host immunity Abundance of immunosuppressive cells in tumor milieu