Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

Else Driehuis; Arne van Hoeck; Kat Moore; Sigrid Kolders; Hayley E Francies; M Can Gulersonmez; Edwin C A Stigter; Boudewijn Burgering; Veerle Geurts; Ana Gracanin; Gergana Bounova; Folkert H Morsink; Robert Vries; Sylvia Boj; Johan van Es; G Johan A Offerhaus; Onno Kranenburg; Mathew J Garnett; Lodewyk Wessels; Edwin Cuppen; Lodewijk A A Brosens; Hans Clevers

doi:10.1073/pnas.1911273116

Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

Else Driehuis, Arne van Hoeck, Kat Moore, Sigrid Kolders, Hayley E Francies, M Can Gulersonmez, Edwin C A Stigter, Boudewijn Burgering, Veerle Geurts, Ana Gracanin, Gergana Bounova, Folkert H Morsink, Robert Vries, Sylvia Boj, Johan van Es, G Johan A Offerhaus, Onno Kranenburg, Mathew J Garnett, Lodewyk Wessels, Edwin CuppenLodewijk A A Brosens, Hans Clevers

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

269 Citations (Scopus)

Abstract

We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.

Original language	English
Journal	Proceedings of the National Academy of Sciences of the United States of America
DOIs	https://doi.org/10.1073/pnas.1911273116
Publication status	E-pub ahead of print - 09 Dec 2019

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Driehuis, E., van Hoeck, A., Moore, K., Kolders, S., Francies, H. E., Gulersonmez, M. C., Stigter, E. C. A., Burgering, B., Geurts, V., Gracanin, A., Bounova, G., Morsink, F. H., Vries, R., Boj, S., van Es, J., Offerhaus, G. J. A., Kranenburg, O., Garnett, M. J., Wessels, L., ... Clevers, H. (2019). Pancreatic cancer organoids recapitulate disease and allow personalized drug screening. Proceedings of the National Academy of Sciences of the United States of America. Advance online publication. https://doi.org/10.1073/pnas.1911273116

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title = "Pancreatic cancer organoids recapitulate disease and allow personalized drug screening",

abstract = "We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.",

author = "Else Driehuis and {van Hoeck}, Arne and Kat Moore and Sigrid Kolders and Francies, {Hayley E} and Gulersonmez, {M Can} and Stigter, {Edwin C A} and Boudewijn Burgering and Veerle Geurts and Ana Gracanin and Gergana Bounova and Morsink, {Folkert H} and Robert Vries and Sylvia Boj and {van Es}, Johan and Offerhaus, {G Johan A} and Onno Kranenburg and Garnett, {Mathew J} and Lodewyk Wessels and Edwin Cuppen and Brosens, {Lodewijk A A} and Hans Clevers",

year = "2019",

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day = "9",

doi = "10.1073/pnas.1911273116",

language = "English",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Driehuis, E, van Hoeck, A, Moore, K, Kolders, S, Francies, HE, Gulersonmez, MC, Stigter, ECA, Burgering, B, Geurts, V, Gracanin, A, Bounova, G, Morsink, FH, Vries, R, Boj, S, van Es, J, Offerhaus, GJA, Kranenburg, O, Garnett, MJ, Wessels, L, Cuppen, E, Brosens, LAA & Clevers, H 2019, 'Pancreatic cancer organoids recapitulate disease and allow personalized drug screening', Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1911273116

TY - JOUR

T1 - Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

AU - Driehuis, Else

AU - van Hoeck, Arne

AU - Moore, Kat

AU - Kolders, Sigrid

AU - Francies, Hayley E

AU - Gulersonmez, M Can

AU - Stigter, Edwin C A

AU - Burgering, Boudewijn

AU - Geurts, Veerle

AU - Gracanin, Ana

AU - Bounova, Gergana

AU - Morsink, Folkert H

AU - Vries, Robert

AU - Boj, Sylvia

AU - van Es, Johan

AU - Offerhaus, G Johan A

AU - Kranenburg, Onno

AU - Garnett, Mathew J

AU - Wessels, Lodewyk

AU - Cuppen, Edwin

AU - Brosens, Lodewijk A A

AU - Clevers, Hans

PY - 2019/12/9

Y1 - 2019/12/9

N2 - We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.

AB - We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.

U2 - 10.1073/pnas.1911273116

DO - 10.1073/pnas.1911273116

M3 - Article

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SN - 0027-8424

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

ER -

Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

Abstract

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