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

1
Department of Neurosciences, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA
2
Department of Cancer Biology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA
3
Department of Surgery, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 6038, USA
4
PamGene International BV, 5200 BJ’s-Hertogenbosch, The Netherlands
5
Neurosciences Institute, ProMedica, Toledo, OH 6038, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8823; https://doi.org/10.3390/ijms21228823
Received: 30 September 2020 / Revised: 16 November 2020 / Accepted: 19 November 2020 / Published: 21 November 2020
(This article belongs to the Special Issue Advances in Kinase Drug Discovery)
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. View Full-Text
Keywords: pancreatic cancer; kinase therapy; fibrosis; desmoplasia; drug discovery; transcription factors; SRC family kinases pancreatic cancer; kinase therapy; fibrosis; desmoplasia; drug discovery; transcription factors; SRC family kinases
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Creeden, J.F.; Alganem, K.; Imami, A.S.; Henkel, N.D.; Brunicardi, F.C.; Liu, S.-H.; Shukla, R.; Tomar, T.; Naji, F.; McCullumsmith, R.E. Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia. Int. J. Mol. Sci. 2020, 21, 8823.

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