CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches

Jiajia Tang; Quan Zheng; Qi Wang; Yaru Zhao; Preeta Ananthanarayanan; Chiara Reina; Berina Šabanović; Ke Jiang; Ming-Hsin Yang; Clara Csilla Meny; Huimin Wang; Mette Ø Agerbaek; Thomas Mandel Clausen; Tobias Gustavsson; Chenlei Wen; Felice Borghi; Alfredo Mellano; Elisabetta Fenocchio; Vanesa Gregorc; Anna Sapino; Thor G Theander; Da Fu; Alexandra Aicher; Ali Salanti; Baiyong Shen; Christopher Heeschen

doi:10.1016/j.xcrm.2024.101692

CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches

Jiajia Tang, Quan Zheng, Qi Wang, Yaru Zhao, Preeta Ananthanarayanan, Chiara Reina, Berina Šabanović, Ke Jiang, Ming-Hsin Yang, Clara Csilla Meny, Huimin Wang, Mette Ø Agerbaek, Thomas Mandel Clausen, Tobias Gustavsson, Chenlei Wen, Felice Borghi, Alfredo Mellano, Elisabetta Fenocchio, Vanesa Gregorc, Anna SapinoThor G Theander, Da Fu, Alexandra Aicher, Ali Salanti, Baiyong Shen, Christopher Heeschen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

6 Citationer (Scopus)

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a "liquid biopsy" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.

Originalsprog	Engelsk
Artikelnummer	101692
Tidsskrift	Cell Reports Medicine
Vol/bind	5
Udgave nummer	9
Antal sider	26
ISSN	2666-3791
DOI	https://doi.org/10.1016/j.xcrm.2024.101692
Status	Udgivet - 2024

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10.1016/j.xcrm.2024.101692Licens: CC BY-NC-ND

FulltextForlagets udgivne version, 62 KBLicens: CC BY-NC-ND

Citationsformater

Tang, J., Zheng, Q., Wang, Q., Zhao, Y., Ananthanarayanan, P., Reina, C., Šabanović, B., Jiang, K., Yang, M.-H., Meny, C. C., Wang, H., Agerbaek, M. Ø., Clausen, T. M., Gustavsson, T., Wen, C., Borghi, F., Mellano, A., Fenocchio, E., Gregorc, V., ... Heeschen, C. (2024). CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches. Cell Reports Medicine, 5(9), Artikel 101692. https://doi.org/10.1016/j.xcrm.2024.101692

Tang, J, Zheng, Q, Wang, Q, Zhao, Y, Ananthanarayanan, P, Reina, C, Šabanović, B, Jiang, K, Yang, M-H, Meny, CC, Wang, H, Agerbaek, MØ , Clausen, TM , Gustavsson, T, Wen, C, Borghi, F, Mellano, A, Fenocchio, E, Gregorc, V, Sapino, A, Theander, TG, Fu, D, Aicher, A, Salanti, A, Shen, B & Heeschen, C 2024, 'CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches', Cell Reports Medicine, bind 5, nr. 9, 101692. https://doi.org/10.1016/j.xcrm.2024.101692

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title = "CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches",

abstract = "Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a {"}liquid biopsy{"} that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.",

keywords = "Humans, Precision Medicine/methods, Pancreatic Neoplasms/pathology, Neoplastic Cells, Circulating/pathology, Carcinoma, Pancreatic Ductal/pathology, Animals, Cell Line, Tumor, Neoplastic Stem Cells/metabolism, Mice, Female, Male, Stearoyl-CoA Desaturase/metabolism, Receptors, CXCR4/metabolism, Middle Aged, Aged, Biomarkers, Tumor/metabolism",

author = "Jiajia Tang and Quan Zheng and Qi Wang and Yaru Zhao and Preeta Ananthanarayanan and Chiara Reina and Berina {\v S}abanovi{\'c} and Ke Jiang and Ming-Hsin Yang and Meny, {Clara Csilla} and Huimin Wang and Agerbaek, {Mette {\O}} and Clausen, {Thomas Mandel} and Tobias Gustavsson and Chenlei Wen and Felice Borghi and Alfredo Mellano and Elisabetta Fenocchio and Vanesa Gregorc and Anna Sapino and Theander, {Thor G} and Da Fu and Alexandra Aicher and Ali Salanti and Baiyong Shen and Christopher Heeschen",

year = "2024",

doi = "10.1016/j.xcrm.2024.101692",

language = "English",

volume = "5",

journal = "Cell Reports Medicine",

issn = "2666-3791",

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T1 - CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches

AU - Tang, Jiajia

AU - Zheng, Quan

AU - Wang, Qi

AU - Zhao, Yaru

AU - Ananthanarayanan, Preeta

AU - Reina, Chiara

AU - Šabanović, Berina

AU - Jiang, Ke

AU - Yang, Ming-Hsin

AU - Meny, Clara Csilla

AU - Wang, Huimin

AU - Agerbaek, Mette Ø

AU - Clausen, Thomas Mandel

AU - Gustavsson, Tobias

AU - Wen, Chenlei

AU - Borghi, Felice

AU - Mellano, Alfredo

AU - Fenocchio, Elisabetta

AU - Gregorc, Vanesa

AU - Sapino, Anna

AU - Theander, Thor G

AU - Fu, Da

AU - Aicher, Alexandra

AU - Salanti, Ali

AU - Shen, Baiyong

AU - Heeschen, Christopher

PY - 2024

Y1 - 2024

N2 - Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a "liquid biopsy" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.

AB - Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a "liquid biopsy" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.

KW - Humans

KW - Precision Medicine/methods

KW - Pancreatic Neoplasms/pathology

KW - Neoplastic Cells, Circulating/pathology

KW - Carcinoma, Pancreatic Ductal/pathology

KW - Animals

KW - Cell Line, Tumor

KW - Neoplastic Stem Cells/metabolism

KW - Mice

KW - Female

KW - Male

KW - Stearoyl-CoA Desaturase/metabolism

KW - Receptors, CXCR4/metabolism

KW - Middle Aged

KW - Aged

KW - Biomarkers, Tumor/metabolism

U2 - 10.1016/j.xcrm.2024.101692

DO - 10.1016/j.xcrm.2024.101692

M3 - Journal article

C2 - 39163864

SN - 2666-3791

VL - 5

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 9

M1 - 101692

ER -