DPY30 loss leads to DNA re-replication and immunoediting in pancreatic ductal adenocarcinoma
WDR5
RBBP5
ASH2L
DPY30
1. DPY30 expression associates with poor prognosis
E
2. In mouse model of PDAC, DPY30 expression associates with tumor grade
Leading Edge of Cancer Research Symposium, Houston, November 17 th –18 th , 2022 Francesca Citron, PharmD, PhD - Draetta Lab, Genomic Medicine
3. DPY30 loss favorites uncoordinated DNA replication
A
B
C
D
4. DPY30 loss induces DNA damage and chromosomal instability
E
F
G
H
I
A
B
C
D
5. DPY30 loss impairs tumor growth only in immune-competent mice
E
F
G
H
I
6. DPY30 knockout tumors display higher CD8+ T cell infiltration and respond better to anti-PD-1
Conclusions: our findings indicate that, in PDAC, DPY30 promotes genome stability, thus providing a rationale for targeting DPY30 or its effector proteins in combination with immune-checkpoint inhibitors. This study is supported by AIRC and the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 800924 and by the 2020 AACR- AstraZeneca START Grant, Grant Number 20-40-12-CITR
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