Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia

Int J Mol Sci. 2020 Nov 21;21(22):8823. doi: 10.3390/ijms21228823.


Kinase drug discovery represents an active area of therapeutic research, with previous pharmaceutical success improving patient outcomes across a wide variety of human diseases. In pancreatic ductal adenocarcinoma (PDAC), innovative pharmaceutical strategies such as kinase targeting have been unable to appreciably increase patient survival. This may be due, in part, to unchecked desmoplastic reactions to pancreatic tumors. Desmoplastic stroma enhances tumor development and progression while simultaneously restricting drug delivery to the tumor cells it protects. Emerging evidence indicates that many of the pathologic fibrotic processes directly or indirectly supporting desmoplasia may be driven by targetable protein tyrosine kinases such as Fyn-related kinase (FRK); B lymphoid kinase (BLK); hemopoietic cell kinase (HCK); ABL proto-oncogene 2 kinase (ABL2); discoidin domain receptor 1 kinase (DDR1); Lck/Yes-related novel kinase (LYN); ephrin receptor A8 kinase (EPHA8); FYN proto-oncogene kinase (FYN); lymphocyte cell-specific kinase (LCK); tec protein kinase (TEC). Herein, we review literature related to these kinases and posit signaling networks, mechanisms, and biochemical relationships by which this group may contribute to PDAC tumor growth and desmoplasia.

Keywords: SRC family kinases; desmoplasia; drug discovery; fibrosis; kinase therapy; pancreatic cancer; transcription factors.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Desmoplastic Small Round Cell Tumor / genetics*
  • Desmoplastic Small Round Cell Tumor / pathology
  • Discoidin Domain Receptor 1 / genetics
  • Disease Progression
  • Humans
  • Neoplasm Proteins / genetics*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-hck / genetics
  • Signal Transduction
  • src-Family Kinases / genetics


  • MAS1 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Mas
  • ARG tyrosine kinase
  • Discoidin Domain Receptor 1
  • Protein-Tyrosine Kinases
  • BLK protein, human
  • FRK protein, human
  • HCK protein, human
  • Proto-Oncogene Proteins c-hck
  • src-Family Kinases