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6 results on '"Gulersonmez, M. Can"'

1. Rifaximin stimulates nitrogen detoxification by PXR-independent mechanisms in human small intestinal organoids

Author

CMM Groep Van Mil, Cancer, CMM Groep Burgering, Child Health, Regenerative Medicine and Stem Cells, CMM, de Wit, Koos, Beuers, Ulrich, Mukha, Anna, Stigter, Edwin, Gulersonmez, M Can, Ramos Pittol, Jose M, Middendorp, Sabine, Takkenberg, R Bart, van Mil, Saskia W C, CMM Groep Van Mil, Cancer, CMM Groep Burgering, Child Health, Regenerative Medicine and Stem Cells, CMM, de Wit, Koos, Beuers, Ulrich, Mukha, Anna, Stigter, Edwin, Gulersonmez, M Can, Ramos Pittol, Jose M, Middendorp, Sabine, Takkenberg, R Bart, and van Mil, Saskia W C

Published
2023

2. Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRASG12D glycolytic colorectal tumors

Author

Ludikhuize, Marlies C, Gevers, Sira, Nguyen, Nguyen T B, Meerlo, Maaike, Roudbari, S Khadijeh Shafiei, Gulersonmez, M Can, Stigter, Edwin C A, Drost, Jarno, Clevers, Hans, Burgering, Boudewijn M T, Rodríguez Colman, Maria J, Ludikhuize, Marlies C, Gevers, Sira, Nguyen, Nguyen T B, Meerlo, Maaike, Roudbari, S Khadijeh Shafiei, Gulersonmez, M Can, Stigter, Edwin C A, Drost, Jarno, Clevers, Hans, Burgering, Boudewijn M T, and Rodríguez Colman, Maria J

Abstract

Despite the fact that 5-fluorouracil (5-FU) is the backbone for chemotherapy in colorectal cancer (CRC), the response rates in patients is limited to 50%. The mechanisms underlying 5-FU toxicity are debated, limiting the development of strategies to improve its efficacy. How fundamental aspects of cancer, such as driver mutations and phenotypic heterogeneity, relate to the 5-FU response remains obscure. This largely relies on the limited number of studies performed in pre-clinical models able to recapitulate the key features of CRC. Here, we analyzed the 5-FU response in patient-derived organoids that reproduce the different stages of CRC. We find that 5-FU induces pyrimidine imbalance, which leads to DNA damage and cell death in the actively proliferating cancer cells deficient in p53. Importantly, p53-deficiency leads to cell death due to impaired cell cycle arrest. Moreover, we find that targeting the Warburg effect in KRASG12D glycolytic tumor organoids enhances 5-FU toxicity by further altering the nucleotide pool and, importantly, without affecting non-transformed WT cells. Thus, p53 emerges as an important factor in determining the 5-FU response, and targeting cancer metabolism in combination with replication stress-inducing chemotherapies emerges as a promising strategy for CRC treatment.

Published
2022

3. Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRAS G12D glycolytic colorectal tumors

Author

CMM Sectie Molecular Cancer Research, CMM Onderwijs, Cancer, CMM Groep Rodriguez Colman, CMM Groep Burgering, CMM, Hubrecht Institute with UMC, Ludikhuize, Marlies C., Gevers, Sira, Nguyen, Nguyen T.B., Meerlo, Maaike, Roudbari, S. Khadijeh Shafiei, Gulersonmez, M. Can, Stigter, Edwin C.A., Drost, Jarno, Clevers, Hans, Burgering, Boudewijn M.T., Rodríguez Colman, Maria J., CMM Sectie Molecular Cancer Research, CMM Onderwijs, Cancer, CMM Groep Rodriguez Colman, CMM Groep Burgering, CMM, Hubrecht Institute with UMC, Ludikhuize, Marlies C., Gevers, Sira, Nguyen, Nguyen T.B., Meerlo, Maaike, Roudbari, S. Khadijeh Shafiei, Gulersonmez, M. Can, Stigter, Edwin C.A., Drost, Jarno, Clevers, Hans, Burgering, Boudewijn M.T., and Rodríguez Colman, Maria J.

Published
2022

4. Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

Author

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

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.

Published
2019

5. Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

Author

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

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.

Published
2019

6. Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

Author

CMM, CMM Groep Cuppen, CMM Groep Burgering, Cancer, CMM Sectie Molecular Cancer Research, Pathologie mortuarium en obductie, Pathologie, Hubrecht Institute with UMC, Pathologie Pathologen staf, CMM Groep Coffer, MS CGO, Regenerative Medicine and Stem Cells, Child Health, Driehuis, Else, Van Hoeck, Arne, Moore, Kat, Kolders, Sigrid, Francies, Hayley E., Gulersonmez, M. Can, Stigter, Edwin C.A., Burgering, Boudewijn, Geurts, Veerle, Gracanin, Ana, Bounova, Gergana, Morsink, Folkert H., Vries, Robert, Boj, Sylvia, Van Es, Johan, Offerhaus, G. Johan A., Kranenburg, Onno, Garnett, Mathew J., Wessels, Lodewyk, Cuppen, Edwin, Brosens, Lodewijk A.A., Clevers, Hans, CMM, CMM Groep Cuppen, CMM Groep Burgering, Cancer, CMM Sectie Molecular Cancer Research, Pathologie mortuarium en obductie, Pathologie, Hubrecht Institute with UMC, Pathologie Pathologen staf, CMM Groep Coffer, MS CGO, Regenerative Medicine and Stem Cells, Child Health, Driehuis, Else, Van Hoeck, Arne, Moore, Kat, Kolders, Sigrid, Francies, Hayley E., Gulersonmez, M. Can, Stigter, Edwin C.A., Burgering, Boudewijn, Geurts, Veerle, Gracanin, Ana, Bounova, Gergana, Morsink, Folkert H., Vries, Robert, Boj, Sylvia, Van Es, Johan, Offerhaus, G. Johan A., Kranenburg, Onno, Garnett, Mathew J., Wessels, Lodewyk, Cuppen, Edwin, Brosens, Lodewijk A.A., and Clevers, Hans

Published
2019

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