Pubblicazioni

Autori:

B, Dreyer Stephan; Rosie, Upstill-Goddard; Viola, Paulus-Hock; Clara, Paris; Eirini-Maria, Lampraki; Eloise, Dray; Bryan, Serrels; Giuseppina, Caligiuri; Selma, Rebus; Dennis, Plenker; Zachary, Galluzzo; Holly, Brunton; Richard, Cunningham; Mathias, Tesson; Craig, Nourse; Ulla-Maja, Bailey; Marc, Jones; Kim, Moran-Jones; W, Wright Derek; Fraser, Duthie; Karin, Oien; Lisa, Evers; J, McKay Colin; A, McGregor Grant; Aditi, Gulati; Rachel, Brough; Ilirjana, Bajrami; Stephan, Pettitt; L, Dziubinski Michele; Juliana, Candido; Frances, Balkwill; T, Barry Simon; Robert, Grützmann; Lola, Rahib; Amber, Johns; Marina, Pajic; E M, Froeling Fieke; Phillip, Beer; A, Musgrove Elizabeth; M, Petersen Gloria; Alan, Ashworth; C, Frame Margaret; C, Crawford Howard; M, Simeone Diane; Chris, Lord; Debabrata, Mukhopadhyay; Christian, Pilarsky; A, Tuveson David; L, Cooke Susanna; B, Jamieson Nigel; P, Morton Jennifer; J, Sansom Owen; J, Bailey Peter; V, Biankin Andrew; K, Chang David; Sarah Allison, Collaborators:; J Bailey, Peter; Bailey, Ulla-Maja; V Biankin, Andrew; Beraldi, Dario; Brunton, Holly; Caligiuri, Giuseppina; Cameron, Euan; K Chang, David; L Cooke, Susanna; Cunningham, Richard; Dreyer, Stephan; Grimwood, Paul; Kelly, Shane; Lampraki, Eirini-Maria; Marshall, John; Martin, Sancha; Mcdade, Brian; Mcelroy, Daniel; A Musgrove, Elizabeth; Nourse, Craig; Paulus-Hock, Viola; Ramsay, Donna; Upstill-Goddard, Rosie; Wright, Derek; D Jones, Marc; Evers, Lisa; Rebus, Selma; Rahib, Lola; Serrels, Bryan; Hair, Jane; B Jamieson, Nigel; J McKay, Colin; Westwood, Paul; Williams, Nicola; Duthie, Fraser; V Biankin, Andrew; Johns, Amber; Mawson, Amanda; K Chang, David; J Scarlett, Christopher; L Brancato, Mary-Anne; J Rowe, Sarah; H Simpson, Skye; Martyn-Smith, Mona; T Thomas, Michelle; A Chantrill, Lorraine; T Chin, Venessa; Chou, Angela; J Cowley, Mark; L Humphris, Jeremy; D Jones, Marc; Scott Mead, R; M Nagrial, Adnan; Pajic, Marina; Pettit, Jessica; Pinese, Mark; Rooman, Ilse; Wu, Jianmin; Tao, Jiang; Dipietro, Renee; Watson, Clare; Steinmann, Angela; Ching Lee, Hong; Wong, Rachel; V Pinho, Andreia; Giry-Laterriere, Marc; J Daly, Roger; A Musgrove, Elizabeth; L Sutherland, Robert; M Grimmond, Sean; Waddell, Nicola; S Kassahn, Karin; K Miller, David; J Wilson, Peter; Patch, Ann-Marie; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Christina; Nones, Katia; Lynn Fink, J; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Newell, Felicity; V Pearson, John; Bailey, Peter; Quinn, Michael; Nagaraj, Shivashankar; Kazakoff, Stephen; Waddell, Nick; Krisnan, Keerthana; Quek, Kelly; Wood, David; S Samra, Jaswinder; J Gill, Anthony; Pavlakis, Nick; Guminski, Alex; Toon, Christopher; Asghari, Ray; D Merrett, Neil; Pavey, Darren; Das, Amitabha; H Cosman, Peter; Ismail, Kasim; O'Connnor, Chelsie; W Lam, Vincent; Mcleod, Duncan; C Pleass, Henry; Richardson, Arthur; James, Virginia; G Kench, James; L Cooper, Caroline; Joseph, David; Sandroussi, Charbel; Crawford, Michael; Gallagher, James; Texler, Michael; Forest, Cindy; Laycock, Andrew; P Epari, Krishna; Ballal, Mo; R Fletcher, David; Mukhedkar, Sanjay; A Spry, Nigel; Deboer, Bastiaan; Chai, Ming; Zeps, Nikolajs; Beilin, Maria; Feeney, Kynan; Q Nguyen, Nan; R Ruszkiewicz, Andrew; Worthley, Chris; P Tan, Chuan; Debrencini, Tamara; Chen, John; E Brooke-Smith, Mark; Papangelis, Virginia; Tang, Henry; P Barbour, Andrew; D Clouston, Andrew; Martin, Patrick; J O'Rourke, Thomas; Chiang, Amy; W Fawcett, Jonathan; Slater, Kellee; Yeung, Shinn; Hatzifotis, Michael; Hodgkinson, Peter; Christophi, Christopher; Nikfarjam, Mehrdad; Mountain, Angela; Cancer Biobank, Victorian; R Eshleman, James; H Hruban, Ralph; Maitra, Anirban; A Iacobuzio-Donahue, Christine; D Schulick, Richard; L Wolfgang, Christopher; A Morgan, Rich

Titolo:

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Anno:

2021

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

No

Nome rivista:

Gastroenterology

ISSN Rivista:

0016-5085

N° Volume:

160

Numero o Fascicolo:

1

Intervallo pagine:

362-377

Parole chiave:

DNA Damage Response; Pancreatic Cancer; Personalized Medicine; Replication Stress

Breve descrizione dei contenuti:

BACKGROUND & AIMS: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. METHODS: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. RESULTS: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P <.001) and PARP inhibitor therapy (P <.001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P <.018) and WEE1 inhibitor (P <.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P <.001) but was not associated with DDR deficiency. CONCLUSIONS: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.

Note:

Supplementary Material: To access the supplementary material accompanying this article, visit the online version of Gastroenterology at www.gastrojournal.org, and at https://doi.org/10.1053/j.gastro.2020.09.043

Id prodotto:

121698

Handle IRIS:

11562/1045585

ultima modifica:

1 febbraio 2025

Citazione bibliografica:

B, Dreyer Stephan; Rosie, Upstill-Goddard; Viola, Paulus-Hock; Clara, Paris; Eirini-Maria, Lampraki; Eloise, Dray; Bryan, Serrels; Giuseppina, Caligiuri; Selma, Rebus; Dennis, Plenker; Zachary, Galluzzo; Holly, Brunton; Richard, Cunningham; Mathias, Tesson; Craig, Nourse; Ulla-Maja, Bailey; Marc, Jones; Kim, Moran-Jones; W, Wright Derek; Fraser, Duthie; Karin, Oien; Lisa, Evers; J, McKay Colin; A, McGregor Grant; Aditi, Gulati; Rachel, Brough; Ilirjana, Bajrami; Stephan, Pettitt; L, Dziubinski Michele; Juliana, Candido; Frances, Balkwill; T, Barry Simon; Robert, Grützmann; Lola, Rahib; Amber, Johns; Marina, Pajic; E M, Froeling Fieke; Phillip, Beer; A, Musgrove Elizabeth; M, Petersen Gloria; Alan, Ashworth; C, Frame Margaret; C, Crawford Howard; M, Simeone Diane; Chris, Lord; Debabrata, Mukhopadhyay; Christian, Pilarsky; A, Tuveson David; L, Cooke Susanna; B, Jamieson Nigel; P, Morton Jennifer; J, Sansom Owen; J, Bailey Peter; V, Biankin Andrew; K, Chang David; Sarah Allison, Collaborators:; J Bailey, Peter; Bailey, Ulla-Maja; V Biankin, Andrew; Beraldi, Dario; Brunton, Holly; Caligiuri, Giuseppina; Cameron, Euan; K Chang, David; L Cooke, Susanna; Cunningham, Richard; Dreyer, Stephan; Grimwood, Paul; Kelly, Shane; Lampraki, Eirini-Maria; Marshall, John; Martin, Sancha; Mcdade, Brian; Mcelroy, Daniel; A Musgrove, Elizabeth; Nourse, Craig; Paulus-Hock, Viola; Ramsay, Donna; Upstill-Goddard, Rosie; Wright, Derek; D Jones, Marc; Evers, Lisa; Rebus, Selma; Rahib, Lola; Serrels, Bryan; Hair, Jane; B Jamieson, Nigel; J McKay, Colin; Westwood, Paul; Williams, Nicola; Duthie, Fraser; V Biankin, Andrew; Johns, Amber; Mawson, Amanda; K Chang, David; J Scarlett, Christopher; L Brancato, Mary-Anne; J Rowe, Sarah; H Simpson, Skye; Martyn-Smith, Mona; T Thomas, Michelle; A Chantrill, Lorraine; T Chin, Venessa; Chou, Angela; J Cowley, Mark; L Humphris, Jeremy; D Jones, Marc; Scott Mead, R; M Nagrial, Adnan; Pajic, Marina; Pettit, Jessica; Pinese, Mark; Rooman, Ilse; Wu, Jianmin; Tao, Jiang; Dipietro, Renee; Watson, Clare; Steinmann, Angela; Ching Lee, Hong; Wong, Rachel; V Pinho, Andreia; Giry-Laterriere, Marc; J Daly, Roger; A Musgrove, Elizabeth; L Sutherland, Robert; M Grimmond, Sean; Waddell, Nicola; S Kassahn, Karin; K Miller, David; J Wilson, Peter; Patch, Ann-Marie; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Christina; Nones, Katia; Lynn Fink, J; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Newell, Felicity; V Pearson, John; Bailey, Peter; Quinn, Michael; Nagaraj, Shivashankar; Kazakoff, Stephen; Waddell, Nick; Krisnan, Keerthana; Quek, Kelly; Wood, David; S Samra, Jaswinder; J Gill, Anthony; Pavlakis, Nick; Guminski, Alex; Toon, Christopher; Asghari, Ray; D Merrett, Neil; Pavey, Darren; Das, Amitabha; H Cosman, Peter; Ismail, Kasim; O'Connnor, Chelsie; W Lam, Vincent; Mcleod, Duncan; C Pleass, Henry; Richardson, Arthur; James, Virginia; G Kench, James; L Cooper, Caroline; Joseph, David; Sandroussi, Charbel; Crawford, Michael; Gallagher, James; Texler, Michael; Forest, Cindy; Laycock, Andrew; P Epari, Krishna; Ballal, Mo; R Fletcher, David; Mukhedkar, Sanjay; A Spry, Nigel; Deboer, Bastiaan; Chai, Ming; Zeps, Nikolajs; Beilin, Maria; Feeney, Kynan; Q Nguyen, Nan; R Ruszkiewicz, Andrew; Worthley, Chris; P Tan, Chuan; Debrencini, Tamara; Chen, John; E Brooke-Smith, Mark; Papangelis, Virginia; Tang, Henry; P Barbour, Andrew; D Clouston, Andrew; Martin, Patrick; J O'Rourke, Thomas; Chiang, Amy; W Fawcett, Jonathan; Slater, Kellee; Yeung, Shinn; Hatzifotis, Michael; Hodgkinson, Peter; Christophi, Christopher; Nikfarjam, Mehrdad; Mountain, Angela; Cancer Biobank, Victorian; R Eshleman, James; H Hruban, Ralph; Maitra, Anirban; A Iacobuzio-Donahue, Christine; D Schulick, Richard; L Wolfgang, Christopher; A Morgan, Rich, Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer «Gastroenterology» , vol. 160 , n. 1 , 2021 , pp. 362-377

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo