MAPK Signaling Pathway: A Central Target in Pancreatic Cancer Therapeutics
Pp. 99-113 (15)
Sanjay K. Srivastava
Pancreatic cancer remains one of the most clinically challenging cancer
despite the advancement in molecular characterization of this disease. Malignancy of
this disease is characterized by the constitutively activated mitogen-activated protein
kinase (MAPK) pathway. The MAPK pathway is activated by growth factors,
mitogens, hormones, cytokines and environmental factors. Activated MAPK induces
expression of downstream genes and regulates cell proliferation, survival,
differentiation, motility, receptor signaling, senescence and transport. Activation of
MAPK in pancreatic cancer is associated with a poor prognosis and results in limited
treatment options. This poor prognosis elicits a need for the development of effective
therapeutic measures to treat and improve pancreatic cancer patient survival. MAPK
targeted pancreatic cancer therapy has been developed in the last few decades with the
use of a number of inhibitors. Inhibitors of RAS, MEK1/2 and ERK1/2 are the main
drugs used pre-clinically and in clinical settings of pancreatic cancer treatment.
Although these inhibitors have shown some clinical benefits, extensive research on the
development of new MAPK signaling pathway inhibitors for the treatment of
pancreatic cancer is warranted.
Inhibitors, MAPK, Pancreatic cancer, Targeted therapy.