Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis

Author:

Vennin Claire12,Chin Venessa T.12ORCID,Warren Sean C.12ORCID,Lucas Morghan C.12ORCID,Herrmann David12ORCID,Magenau Astrid12,Melenec Pauline12ORCID,Walters Stacey N.12ORCID,del Monte-Nieto Gonzalo23ORCID,Conway James R. W.12,Nobis Max12ORCID,Allam Amr H.12,McCloy Rachael A.12ORCID,Currey Nicola12,Pinese Mark12ORCID,Boulghourjian Alice1,Zaratzian Anaiis1,Adam Arne A. S.3,Heu Celine4,Nagrial Adnan M.1,Chou Angela125,Steinmann Angela1,Drury Alison1ORCID,Froio Danielle1,Giry-Laterriere Marc12ORCID,Harris Nathanial L. E.16,Phan Tri12ORCID,Jain Rohit78,Weninger Wolfgang789,McGhee Ewan J.10,Whan Renee3ORCID,Johns Amber L.1111213,Samra Jaswinder S.101314,Chantrill Lorraine11314,Gill Anthony J.111121315ORCID,Kohonen-Corish Maija1216,Harvey Richard P.2317,Biankin Andrew V.131819ORCID,Evans T. R. Jeffry10,Anderson Kurt I.10,Grey Shane T.12,Ormandy Christopher J.12ORCID,Gallego-Ortega David12ORCID,Wang Yingxiao20,Samuel Michael S.21ORCID,Sansom Owen J.10,Burgess Andrew12ORCID,Cox Thomas R.12ORCID,Morton Jennifer P.10ORCID,Pajic Marina12,Timpson Paul12,

Affiliation:

1. The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.

2. St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.

3. Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.

4. Biomedical Imaging Facility, Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.

5. Department of Pathology, St. Vincent’s Hospital, Sydney, New South Wales 2010, Australia.

6. Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales 2522, Australia.

7. Immune Imaging Program, Centenary Institute, University of Sydney, Sydney, New South Wales 2006, Australia.

8. University of Sydney Medical School, Sydney, New South Wales 2006, Australia.

9. Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.

10. Cancer Research UK Beatson Institute, Glasgow, Scotland G61 BD, U.K.

11. Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research and Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.

12. University of Sydney, Sydney, New South Wales 2006, Australia.

13. Australian Pancreatic Cancer Genome Initiative

14. Department of Surgery, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.

15. Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, New South Wales 2560, Australia.

16. School of Medicine, Western Sydney University, Penrith, Sydney, New South Wales 2751, Australia.

17. School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, New South Wales 2052, Australia.

18. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Scotland G61 BD, U.K.

19. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Scotland G61 BD, U.K.

20. Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, San Diego, CA 92121, USA.

21. Centre for Cancer Biology, SA Pathology and University of South Australia School of Medicine, University of Adelaide, Adelaide, South Australia 5000, Australia.

Abstract

Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy and impairs metastatic spread in pancreatic cancer.

Funder

National Health and Medical Research Council

Cancer Council NSW

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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