TY - JOUR
T1 - Cyclooxygenase-2 and cancer treatment
T2 - Understanding the risk should be worth the reward
AU - Menter, David G.
AU - Schilsky, Richard L.
AU - DuBois, Raymond N.
PY - 2010/3/1
Y1 - 2010/3/1
N2 - Targeting the prostaglandin (PG) pathway is potentially a critical intervention for the prevention and treatment of cancer. Central to PG biosynthesis are two isoforms of cyclooxygenase (COX 1 and 2), which produce prostaglandin H2 (PGH2) from plasma membrane stores of fatty acids. COX-1 is constitutively expressed, whereas COX-2 is an inducible isoform upregulated in many cancers. Differences between COX-1 and COX-2 catalytic sites enabled development of selective inhibitors. Downstream of the COX enzymes, prostaglandin E2 synthase converts available PGH 2 to prostaglandin E2 (PGE2), which can stimulate cancer progression. Significant research efforts are helping identify more selective targets and fully elucidate the downstream targets of prostaglandin E2-mediated oncogenesis. Nonetheless, as a key ratelimiting control point of PG biosynthesis, COX-2 continues to be an important anticancer target. As we embark upon a new era of individualized medicine, a better understanding of the individual risk and/or benefit involved in COX-2 selective targeting is rapidly evolving. This review endeavors to summarize developments in our understanding of COX-2 and its downstream targets as vital areas of anticancer research and to provide the current status of an exciting aspect of molecular medicine.
AB - Targeting the prostaglandin (PG) pathway is potentially a critical intervention for the prevention and treatment of cancer. Central to PG biosynthesis are two isoforms of cyclooxygenase (COX 1 and 2), which produce prostaglandin H2 (PGH2) from plasma membrane stores of fatty acids. COX-1 is constitutively expressed, whereas COX-2 is an inducible isoform upregulated in many cancers. Differences between COX-1 and COX-2 catalytic sites enabled development of selective inhibitors. Downstream of the COX enzymes, prostaglandin E2 synthase converts available PGH 2 to prostaglandin E2 (PGE2), which can stimulate cancer progression. Significant research efforts are helping identify more selective targets and fully elucidate the downstream targets of prostaglandin E2-mediated oncogenesis. Nonetheless, as a key ratelimiting control point of PG biosynthesis, COX-2 continues to be an important anticancer target. As we embark upon a new era of individualized medicine, a better understanding of the individual risk and/or benefit involved in COX-2 selective targeting is rapidly evolving. This review endeavors to summarize developments in our understanding of COX-2 and its downstream targets as vital areas of anticancer research and to provide the current status of an exciting aspect of molecular medicine.
UR - http://www.scopus.com/inward/record.url?scp=77649090075&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649090075&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-09-0788
DO - 10.1158/1078-0432.CCR-09-0788
M3 - Review article
C2 - 20179228
AN - SCOPUS:77649090075
SN - 1078-0432
VL - 16
SP - 1384
EP - 1390
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -