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WEE1-targeted cell-cycle
vulnerabilities
•
In SCLC cells, combined
loss of RB1 and TP53
result in
increased cell survival
•
WEE1 kinase inhibitor
induces
G2 arrest
•
Combination
of a
WEE1 inhibitor
with
DNA-damaging
agents
(antimetabolites, topisomerase inh., platinum agents and
PARP inh)
results in synergistic efficacy in
TP53-deficient
tumors
•
Several Phase II studies
ongoing with WEE1 inh.
AZD1775
+/- carboplatin (NCT02593019, NCT02937818)
•
TP53/RB1 status
and
WEE1 expression
as
Biomarkers
?
Sabari J, Nat Rev Clin Oncol 2017