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Targeting the cyclin D1-CDK 4/6 pathway: rationale
The CDK 4/6-cyclin D1-E2F pathway
CDK 4/6
Cyclin D
(ER/PR/AR)
Wnt/b-catenin
MAPKs
STATs
PI3K/AKT
NF-kB
p53
p21
p16
RB
P
E2F
RB
E2F
G1
M
G2
G0
S
Gene transcription
(Tumor suppressor)
Data from Musgrove EA, et al.
Nat Rev Cancer
. 2011;11(8):558-572.
•
The growth of ER+ breast cancer
is dependent on Cyclin D1-
CDK4/6
•
Multiple activators of cyclin D1
expression
–
CCND1
amplification
–
ER signaling
–
Mitogenic signaling