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University of Groningen Exploiting genomic instability as an Achilles’ heel in cancer Guerrero Llobet, Sergi

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University of Groningen

Exploiting genomic instability as an Achilles’ heel in cancer

Guerrero Llobet, Sergi

DOI:

10.33612/diss.168484998

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from

it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date:

2021

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Guerrero Llobet, S. (2021). Exploiting genomic instability as an Achilles’ heel in cancer. University of

Groningen. https://doi.org/10.33612/diss.168484998

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Exploiting genomic instability as

an Achilles’ heel in cancer

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The studies described in this thesis were performed at the Department of Medical Oncology of the University Medical Center Groningen in Groningen, The Netherlands.

Cover: Ariadna Vaz

lay-out design: S. Guerrero & H.R. de Boer

Copyright © 2021, S. Guerrero

All rights reserved. No part of this thesis may be reproduced, stored or transmitted in any form or by any means without permission of the author

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Exploiting genomic instability as

an Achilles’ heel in cancer

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the

Rector Magnificus Prof. C. Wijmenga and

in accordance with

the decision by the College of Deans.

This thesis will be defended in public on

Wednesday 19 May 2021 at 9 hours

by

Sergi Guerrero Llobet

born on 5 January 1989

in Barcelona

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Promotor

Prof. M.A.T.M. van Vugt

Co-promotor

Prof. R.S.N. Fehrmann

Assessment Committee

Prof. S. de Jong

Prof. R. Brakenhoff

Prof. F. Foijer

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Table of contents

Chapter 1 General introduction and outline of the thesis

7

Chapter 2 Replication Stress: Driver and therapeutic target in

genomically instable cancers

Advances in Protein Chemistry and Structural Biology

(2019) 115:

157-201

13

Chapter 3 Cyclin E expression is associated with high levels of

replication stress in triple-negative breast cancer

npj Breast Cancer

(2020) 6: 40

47

Chapter 4 Overexpression of Cyclin E1 or Cdc25A leads to

replication stress,mitotic aberrancies, and increased

sensitivity to replication checkpoint inhibitors

Oncogenesis

(2020) 9 (10): 88

79

Chapter 5 An mRNA expression-based signature for

oncogene-induced replication-stress

Submitted

109

Chapter 6 Discussion and summary

131

Appendix

Nederlandse samenvatting

141

Curriculum Vitae and Publications

144

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