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1,162 results on '"Voest, Emile E."'

152. Codon-specific KRASmutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer

Author

van de Haar, Joris, Ma, Xuhui, Ooft, Salo N., van der Helm, Pim W., Hoes, Louisa R., Mainardi, Sara, Pinato, David J., Sun, Kristi, Salvatore, Lisa, Tortora, Giampaolo, Zurlo, Ina Valeria, Leo, Silvana, Giampieri, Riccardo, Berardi, Rossana, Gelsomino, Fabio, Merz, Valeria, Mazzuca, Federica, Antonuzzo, Lorenzo, Rosati, Gerardo, Stavraka, Chara, Ross, Paul, Rodriquenz, Maria Grazia, Pavarana, Michele, Messina, Carlo, Iveson, Timothy, Zoratto, Federica, Thomas, Anne, Fenocchio, Elisabetta, Ratti, Margherita, Depetris, Ilaria, Cergnul, Massimiliano, Morelli, Cristina, Libertini, Michela, Parisi, Alessandro, De Tursi, Michele, Zanaletti, Nicoletta, Garrone, Ornella, Graham, Janet, Longarini, Raffaella, Gobba, Stefania Maria, Petrillo, Angelica, Tamburini, Emiliano, La Verde, Nicla, Petrelli, Fausto, Ricci, Vincenzo, Wessels, Lodewyk F. A., Ghidini, Michele, Cortellini, Alessio, Voest, Emile E., and Valeri, Nicola

Abstract

Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic colorectal cancer (mCRC) treated with the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAScodon G12 (KRASG12) mutations as a potential biomarker of resistance. Next, we collected real-world data of 960 patients with mCRC receiving FTD/TPI and validated that KRASG12mutations were significantly associated with poor survival, also in analyses restricted to the RAS/RAFmutant subgroup. We next analyzed the data of the global, double-blind, placebo-controlled, phase 3 RECOURSE trial (n= 800 patients) and found that KRASG12mutations (n= 279) were predictive biomarkers for reduced overall survival (OS) benefit of FTD/TPI versus placebo (unadjusted interaction P= 0.0031, adjusted interaction P= 0.015). For patients with KRASG12mutations in the RECOURSE trial, OS was not prolonged with FTD/TPI versus placebo (n= 279; hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.73–1.20; P= 0.85). In contrast, patients with KRASG13mutant tumors showed significantly improved OS with FTD/TPI versus placebo (n= 60; HR = 0.29; 95% CI = 0.15–0.55; P< 0.001). In isogenic cell lines and patient-derived organoids, KRASG12mutations were associated with increased resistance to FTD-based genotoxicity. In conclusion, these data show that KRASG12mutations are biomarkers for reduced OS benefit of FTD/TPI treatment, with potential implications for approximately 28% of patients with mCRC under consideration for treatment with FTD/TPI. Furthermore, our data suggest that genomics-based precision medicine may be possible for a subset of chemotherapies.

Published
2023
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157. Detailed imaging and genetic analysis reveal a secondary BRAFL505H resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib

Author

Hoogstraat, Marlous, Gadellaa-van Hooijdonk, Christa G., Ubink, Inge, Besselink, Nicolle J. M., Pieterse, Mark, Veldhuis, Wouter, van Stralen, Marijn, Meijer, Eelco F. J., Willems, Stefan M., Hadders, Michael A., Kuilman, Thomas, Krijgsman, Oscar, Peeper, Daniel S., Koudijs, Marco J., Cuppen, Edwin, Voest, Emile E., and Lolkema, Martijn P.

Published
2015
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160. Feasibility of whole-genome sequencing in routine clinical practice.

Author

Samsom, Kris, primary, Monkhorst, Kim, additional, Schipper, Luuk J., additional, Roepman, Paul, additional, Bosch, Linda J.W., additional, de Bruijn, Ewart, additional, Riethorst, Immy, additional, Schoenmaker, Lieke, additional, Van Der Kolk, Lizet, additional, Buffart, Tineke, additional, van der Hoeven, Jacobus J.M., additional, Cuppen, Edwin P.J.G., additional, Voest, Emile E., additional, and Meijer, Gerrit A., additional

Published
2021
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161. Whole-genome sequencing to improve sarcoma diagnosis and patient care.

Author

Schipper, Luuk J., primary, Monkhorst, Kim, additional, Samsom, Kris, additional, Snaebjornsson, Petur, additional, Van Boven, Hester, additional, Roepman, Paul, additional, Van Der Kolk, Lizet, additional, Bosch, Linda J.W., additional, van Houdt, Winan J., additional, Van Der Graaf, Winette T.A., additional, Meijer, Gerrit A., additional, and Voest, Emile E., additional

Published
2021
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162. Extension of Indication for Authorised Oncology Products in the European Union: A Joint Effort of Multiple Stakeholders

Author

Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Mulder, Jorn, Verjans, Robin, Verbaanderd, Ciska, Pean, Elias, Weemers, Just, Leufkens, Hubert G.M., Pignatti, Francesco, de Boer, Anthonius, Voest, Emile E., Stoyanova-Beninska, Violeta V., Pasmooij, Anna M.G., Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Mulder, Jorn, Verjans, Robin, Verbaanderd, Ciska, Pean, Elias, Weemers, Just, Leufkens, Hubert G.M., Pignatti, Francesco, de Boer, Anthonius, Voest, Emile E., Stoyanova-Beninska, Violeta V., and Pasmooij, Anna M.G.

Published
2021

163. Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma

Author

Dijkstra, Krijn K., van den Berg, José G., Weeber, Fleur, van de Haar, Joris, Velds, Arno, Kaing, Sovann, Peters, Dennis D.G.C., Eskens, Ferry A.L.M., de Groot, Derk Jan A., Tesselaar, Margot E.T., Voest, Emile E., Dijkstra, Krijn K., van den Berg, José G., Weeber, Fleur, van de Haar, Joris, Velds, Arno, Kaing, Sovann, Peters, Dennis D.G.C., Eskens, Ferry A.L.M., de Groot, Derk Jan A., Tesselaar, Margot E.T., and Voest, Emile E.

Abstract

Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly understood disease with limited treatment options. A better understanding of this disease would greatly benefit from the availability of representative preclinical models. Here, we present the potential of tumor organoids, three-dimensional cultures of tumor cells, to model GEP-NEC. We established three GEP-NEC organoid lines, originating from the stomach and colon, and characterized them using DNA sequencing and immunohistochemistry. Organoids largely resembled the original tumor in expression of synaptophysin, chromogranin and Ki-67. Models derived from tumors containing both neuroendocrine and non-neuroendocrine components were at risk of overgrowth by non-neuroendocrine tumor cells. Organoids were derived from patients treated with cisplatin and everolimus and for the three patients studied, organoid chemosensitivity paralleled clinical response. We demonstrate the feasibility of establishing NEC organoid lines and their potential applications. Organoid culture has the potential to greatly extend the repertoire of preclinical models for GEP-NEC, supporting drug development for this difficult-to-treat tumor type.

Published
2021

164. Patients with bi-allelic BRCA1/2 inactivation respond to olaparib treatment across histologic tumor types

Author

Pathologie Pathologen staf, Cancer, Pathologie Moleculair, van der Wijngaart, Hanneke, Hoes, Louisa R, van Berge Henegouwen, J Maxime, van der Velden, Daphne L, Zeverijn, Laurien J, Roepman, Paul, van Werkhoven, Erik, de Leng, Wendy W J, Jansen, Anne M L, Mehra, Niven, Robbrecht, Debbie G J, Labots, Mariette, de Groot, Derk Jan A, Hoeben, Ann, Hamberg, Paul, Gelderblom, Hans, Voest, Emile E, Verheul, Henk M W, Pathologie Pathologen staf, Cancer, Pathologie Moleculair, van der Wijngaart, Hanneke, Hoes, Louisa R, van Berge Henegouwen, J Maxime, van der Velden, Daphne L, Zeverijn, Laurien J, Roepman, Paul, van Werkhoven, Erik, de Leng, Wendy W J, Jansen, Anne M L, Mehra, Niven, Robbrecht, Debbie G J, Labots, Mariette, de Groot, Derk Jan A, Hoeben, Ann, Hamberg, Paul, Gelderblom, Hans, Voest, Emile E, and Verheul, Henk M W

Published
2021

167. Cytosolic p120-catenin regulates growth of metastatic lobular carcinoma through Rock1-mediated anoikis resistance

Author

Schackmann, Ron C.J., van Amersfoort, Miranda, Haarhuis, Judith H.I., Vlug, Eva J., Halim, Vincentius A., Roodhart, Jeanine M.L., Vermaat, Joost S., Voest, Emile E., van der Groep, Petra, van Diest, Paul J., Jonkers, Jos, and Derksen, Patrick W.B.

Subjects
Cadherins -- Physiological aspects -- Research, Cellular signal transduction -- Research, Breast cancer -- Development and progression -- Research, Health care industry
Abstract

Metastatic breast cancer is the major cause of cancer-related death among women in the Western world. Invasive carcinoma cells are able to counteract apoptotic signals in the absence of anchorage, enabling cell survival during invasion and dissemination. Although loss of E-cadherin is a cardinal event in the development and progression of invasive lobular carcinoma (ILC), little is known about the underlying mechanisms that govern these processes. Using a mouse model of human ILC, we show here that cytosolic p120-catenin (p120) regulates tumor growth upon loss of E-cadherin through the induction of anoikis resistance. p120 conferred anchorage independence by indirect activation of Rho/Rock signaling through interaction and inhibition of myosin phosphatase Rho-interacting protein (Mrip), an antagonist of Rho/Rock function. Consistent with these data, primary human ILC samples expressed hallmarks of active Rock signaling, and Rock controlled the anoikis resistance of human ILC cells. Thus, we have linked loss of E-cadherin--an initiating event in ILC development--to Rho/Rock-mediated control of anchorage-independent survival. Because activation of Rho and Rock are strongly linked to cancer progression and are susceptible to pharmacological inhibition, these insights may have clinical implications for the development of tailor-made intervention strategies to better treat invasive and metastatic lobular breast cancer., Introduction Breast cancer progression depends on the capacity of cells to invade, metastasize, and colonize distant sites. Loss of tumor cell adhesion and subsequent anchorage-independent survival are crucial steps in [...]

Published
2011
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168. Rapid Chemotherapy-Induced Acute Endothelial Progenitor Cell Mobilization: Implications for Antiangiogenic Drugs as Chemosensitizing Agents

Author

Shaked, Yuval, Henke, Erik, Roodhart, Jeanine M.L., Mancuso, Patrizia, Langenberg, Marlies H.G., Colleoni, Marco, Daenen, Laura G., Man, Shan, Xu, Ping, Emmenegger, Urban, Tang, Terence, Zhu, Zhenping, Witte, Larry, Strieter, Robert M., Bertolini, Francesco, Voest, Emile E., Benezra, Robert, and Kerbel, Robert S.

Published
2008
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170. γδ T cells are effectors of immunotherapy in cancers with HLA class I defects

Author

de Vries, Natasja L., van de Haar, Joris, Veninga, Vivien, Chalabi, Myriam, Ijsselsteijn, Marieke E., van der Ploeg, Manon, van den Bulk, Jitske, Ruano, Dina, van den Berg, Jose G., Haanen, John B., Zeverijn, Laurien J., Geurts, Birgit S., de Wit, Gijs F., Battaglia, Thomas W., Gelderblom, Hans, Verheul, Henk M. W., Schumacher, Ton N., Wessels, Lodewyk F. A., Koning, Frits, de Miranda, Noel F. C. C., and Voest, Emile E.

Abstract

DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB)1,2. Here, in contrast to other cancer types3–5, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8+T cells in this context. We next identified a strong association between B2Minactivation and increased infiltration by γδ T cells in MMR-d cancers. These γδ T cells mainly comprised the Vδ1 and Vδ3 subsets, and expressed high levels of PD-1, other activation markers, including cytotoxic molecules, and a broad repertoire of killer-cell immunoglobulin-like receptors. In vitro, PD-1+γδ T cells that were isolated from MMR-d colon cancers exhibited enhanced reactivity to human leukocyte antigen (HLA)-class-I-negative MMR-d colon cancer cell lines and B2M-knockout patient-derived tumour organoids compared with antigen-presentation-proficient cells. By comparing paired tumour samples from patients with MMR-d colon cancer that were obtained before and after dual PD-1 and CTLA-4 blockade, we found that immune checkpoint blockade substantially increased the frequency of γδ T cells in B2M-deficient cancers. Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy.

Published
2023
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171. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer

Author

Tol, Jolien, Koopman, Miriam, Cats, Annemieke, Rodenburg, Cees J., Creemers, Geert J.M., Schrama, Jolanda G., Erdkamp, Frans L.G., Vos, Allert H., van Groeningen, Cees J., Sinnige, Harm A.M., Richel, Dirk J., Voest, Emile E., Dijkstra, Jeroen R., Vink-Borger, Marianne E., Antonini, Ninja F., Mol, Linda, van Kriekan, Johan H.J.M., Dalesio, Otilia, and Punt, Cornelis J.A.

Subjects
Colorectal cancer -- Care and treatment, Chemotherapy -- Usage, Chemotherapy -- Health aspects, Cancer -- Chemotherapy, Cancer -- Usage, Cancer -- Health aspects
Abstract

A study was conducted to evaluate the effect of addition of cetuximab to bevacizumab and chemotherapy in the treatment of metastatic colorectal cancer. Results indicated that the addition of cetuximab to the prescribed treatment resulted in a poorer quality of life and increased the risk of adverse effects among patients with colorectal cancer.

Published
2009

173. Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma

Author

Dijkstra, Krijn K., primary, van den Berg, José G., additional, Weeber, Fleur, additional, van de Haar, Joris, additional, Velds, Arno, additional, Kaing, Sovann, additional, Peters, Dennis D. G. C., additional, Eskens, Ferry A. L. M., additional, de Groot, Derk-Jan A., additional, Tesselaar, Margot E. T., additional, and Voest, Emile E., additional

Published
2021
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174. Additional file 2 of Study protocol: Whole genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE)

Author

Samsom, Kris G., Bosch, Linda J. W., Schipper, Luuk J., Roepman, Paul, Ewart De Bruijn, Hoes, Louisa R., Immy Riethorst, Schoenmaker, Lieke, Kolk, Lizet E. Van Der, Retèl, Valesca P., Frederix, Geert W. J., Buffart, Tineke E., Hoeven, Jacobus J. M. Van Der, Voest, Emile E., Cuppen, Edwin, Monkhorst, Kim, and Meijer, Gerrit A.

Abstract

Additional file 2: Questionnaire halfway.

Published
2020
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175. Additional file 1 of Study protocol: Whole genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE)

Author

Samsom, Kris G., Bosch, Linda J. W., Schipper, Luuk J., Roepman, Paul, Ewart De Bruijn, Hoes, Louisa R., Immy Riethorst, Schoenmaker, Lieke, Kolk, Lizet E. Van Der, Retèl, Valesca P., Frederix, Geert W. J., Buffart, Tineke E., Hoeven, Jacobus J. M. Van Der, Voest, Emile E., Cuppen, Edwin, Monkhorst, Kim, and Meijer, Gerrit A.

Abstract

Additional file 1: Questionnaire at start of study.

Published
2020
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177. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers

Author

Chalabi, Myriam, Chalabi, Myriam, Fanchi, Lorenzo F., Dijkstra, Krijn K., van den Berg, Jose G., Aalbers, Arend G., Sikorska, Karolina, Lopez-Yurda, Marta, Grootscholten, Cecile, Beets, Geerard L., Snaebjornsson, Petur, Maas, Monique, Mertz, Marjolijn, Veninga, Vivien, Bounova, Gergana, Broeks, Annegien, Beets-Tan, Regina G., de Wijkerslooth, Thomas R., van Lent, Anja U., Marsman, Hendrik A., Nuijten, Elvira, Kok, Niels F., Kuiper, Maria, Verbeek, Wieke H., Kok, Marleen, Van Leerdam, Monique E., Schumacher, Ton N., Voest, Emile E., Haanen, John B., Chalabi, Myriam, Chalabi, Myriam, Fanchi, Lorenzo F., Dijkstra, Krijn K., van den Berg, Jose G., Aalbers, Arend G., Sikorska, Karolina, Lopez-Yurda, Marta, Grootscholten, Cecile, Beets, Geerard L., Snaebjornsson, Petur, Maas, Monique, Mertz, Marjolijn, Veninga, Vivien, Bounova, Gergana, Broeks, Annegien, Beets-Tan, Regina G., de Wijkerslooth, Thomas R., van Lent, Anja U., Marsman, Hendrik A., Nuijten, Elvira, Kok, Niels F., Kuiper, Maria, Verbeek, Wieke H., Kok, Marleen, Van Leerdam, Monique E., Schumacher, Ton N., Voest, Emile E., and Haanen, John B.

Abstract

PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86-100%) dMMR tumors, with 19 major pathological responses (MPRs

Published
2020

178. Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine

Author

Dijkstra, Krijn K, Monkhorst, Kim, Schipper, Luuk J, Hartemink, Koen J, Smit, Egbert F, Kaing, Sovann, de Groot, Rosa, Wolkers, Monika C, Clevers, Hans, Cuppen, Edwin, Voest, Emile E, Dijkstra, Krijn K, Monkhorst, Kim, Schipper, Luuk J, Hartemink, Koen J, Smit, Egbert F, Kaing, Sovann, de Groot, Rosa, Wolkers, Monika C, Clevers, Hans, Cuppen, Edwin, and Voest, Emile E

Abstract

Clinical implementation of tumor organoids for personalized medicine requires that pure tumor organoids can be reliably established. Here, we present our experience with organoid cultures from >70 non-small cell lung cancer (NSCLC) samples. We systematically evaluate several methods to identify tumor purity of organoids established from intrapulmonary tumors. Eighty percent of organoids from intrapulmonary lesions have a normal copy number profile, suggesting overgrowth by normal airway organoids (AOs). This is further supported by the failure to detect mutations found in the original tumor in organoids. Histomorphology alone is insufficient to determine tumor purity, but when combined with p63 immunostaining, tumor and normal AOs can be distinguished. Taking into account overgrowth by normal AOs, the establishment rate of pure NSCLC organoids is 17%. Therefore, current methods are insufficient to establish pure NSCLC organoids from intrapulmonary lesions. We discourage their use unless steps are taken to prevent overgrowth by normal AOs.

Published
2020

179. Study protocol:Whole genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE)

Author

Samsom, Kris G, Bosch, Linda J W, Schipper, Luuk J, Roepman, Paul, de Bruijn, Ewart, Hoes, Louisa R, Riethorst, Immy, Schoenmaker, Lieke, van der Kolk, Lizet E, Retèl, Valesca P, Frederix, Geert W J, Buffart, Tineke E, van der Hoeven, Jacobus J M, Voest, Emile E, Cuppen, Edwin, Monkhorst, Kim, Meijer, Gerrit A, Samsom, Kris G, Bosch, Linda J W, Schipper, Luuk J, Roepman, Paul, de Bruijn, Ewart, Hoes, Louisa R, Riethorst, Immy, Schoenmaker, Lieke, van der Kolk, Lizet E, Retèl, Valesca P, Frederix, Geert W J, Buffart, Tineke E, van der Hoeven, Jacobus J M, Voest, Emile E, Cuppen, Edwin, Monkhorst, Kim, and Meijer, Gerrit A

Abstract

BACKGROUND: 'Precision oncology' can ensure the best suitable treatment at the right time by tailoring treatment towards individual patient and comprehensive tumour characteristics. In current molecular pathology, diagnostic tests which are part of the standard of care (SOC) only cover a limited part of the spectrum of genomic changes, and often are performed in an iterative way. This occurs at the expense of valuable patient time, available tissue sample, and interferes with 'first time right' treatment decisions. Whole Genome Sequencing (WGS) captures a near complete view of genomic characteristics of a tumour in a single test. Moreover, WGS facilitates faster implementation of new treatment relevant biomarkers. At present, WGS mainly has been applied in study settings, but its performance in a routine diagnostic setting remains to be evaluated. The WIDE study aims to investigate the feasibility and validity of WGS-based diagnostics in clinical practice.METHODS: 1200 consecutive patients in a single comprehensive cancer centre with (suspicion of) a metastasized solid tumour will be enrolled with the intention to analyse tumour tissue with WGS, in parallel to SOC diagnostics. Primary endpoints are (1) feasibility of implementation of WGS-based diagnostics into routine clinical care and (2) clinical validation of WGS by comparing identification of treatment-relevant variants between WGS and SOC molecular diagnostics. Secondary endpoints entail (1) added clinical value in terms of additional treatment options and (2) cost-effectiveness of WGS compared to SOC diagnostics through a Health Technology Assessment (HTA) analysis. Furthermore, the (3) perceived impact of WGS-based diagnostics on clinical decision making will be evaluated through questionnaires. The number of patients included in (experimental) therapies initiated based on SOC or WGS diagnostics will be reported with at least 3 months follow-up. The clinical efficacy is beyond the scope of WIDE. Ke

Published
2020

180. BTK inhibitors synergise with 5-FU to treat drug-resistant TP53-null colon cancers

Author

Lavitrano, M, Ianzano, L, Bonomo, S, Cialdella, A, Cerrito, M, Pisano, F, Missaglia, C, Giovannoni, R, Romano, G, Mclean, C, Voest, E, D'Amato, F, Noli, B, Ferri, G, Agostini, M, Pucciarelli, S, Helin, K, Leone, B, Canzonieri, V, Grassilli, E, Lavitrano, Marialuisa, Ianzano, Leonarda, Bonomo, Sara, Cialdella, Annamaria, Cerrito, Maria Grazia, Pisano, Fabio, Missaglia, Carola, Giovannoni, Roberto, Romano, Gabriele, McLean, Chelsea M, Voest, Emile E, D'Amato, Filomena, NOLI, BARBARA, Ferri, Gian Luca, Agostini, Marco, Pucciarelli, Salvatore, Helin, Kristian, Leone, Biagio Eugenio, Canzonieri, Vincenzo, Grassilli, Emanuela, Lavitrano, M, Ianzano, L, Bonomo, S, Cialdella, A, Cerrito, M, Pisano, F, Missaglia, C, Giovannoni, R, Romano, G, Mclean, C, Voest, E, D'Amato, F, Noli, B, Ferri, G, Agostini, M, Pucciarelli, S, Helin, K, Leone, B, Canzonieri, V, Grassilli, E, Lavitrano, Marialuisa, Ianzano, Leonarda, Bonomo, Sara, Cialdella, Annamaria, Cerrito, Maria Grazia, Pisano, Fabio, Missaglia, Carola, Giovannoni, Roberto, Romano, Gabriele, McLean, Chelsea M, Voest, Emile E, D'Amato, Filomena, NOLI, BARBARA, Ferri, Gian Luca, Agostini, Marco, Pucciarelli, Salvatore, Helin, Kristian, Leone, Biagio Eugenio, Canzonieri, Vincenzo, and Grassilli, Emanuela

Abstract

Colorectal cancer (CRC) is the fourth cause of death from cancer worldwide mainly due to the high incidence of drug-resistance. During a screen for new actionable targets in drug-resistant tumours we recently identified p65BTK – a novel oncogenic isoform of Bruton's tyrosine kinase. Studying three different cohorts of patients here we show that p65BTK expression correlates with histotype and cancer progression. Using drug-resistant TP53-null colon cancer cells as a model we demonstrated that p65BTK silencing or chemical inhibition overcame the 5-fluorouracil resistance of CRC cell lines and patient-derived organoids and significantly reduced the growth of xenografted tumours. Mechanistically, we show that blocking p65BTK in drug-resistant cells abolished a 5-FU-elicited TGFB1 protective response and triggered E2F-dependent apoptosis. Taken together, our data demonstrated that targeting p65BTK restores the apoptotic response to chemotherapy of drug-resistant CRCs and gives a proof-of-concept for suggesting the use of BTK inhibitors in combination with 5-FU as a novel therapeutic approach in CRC patients. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2020

181. Study protocol: Whole genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE)

Author

CMM Groep Cuppen, HEE, Child Health, JC onderzoeksprogramma Methodologie, Externen Med. Onco, CMM, Cancer, Pathologie Groep Van Diest, Samsom, Kris G, Bosch, Linda J W, Schipper, Luuk J, Roepman, Paul, de Bruijn, Ewart, Hoes, Louisa R, Riethorst, Immy, Schoenmaker, Lieke, van der Kolk, Lizet E, Retèl, Valesca P, Frederix, Geert W J, Buffart, Tineke E, van der Hoeven, Jacobus J M, Voest, Emile E, Cuppen, Edwin, Monkhorst, Kim, Meijer, Gerrit A, CMM Groep Cuppen, HEE, Child Health, JC onderzoeksprogramma Methodologie, Externen Med. Onco, CMM, Cancer, Pathologie Groep Van Diest, Samsom, Kris G, Bosch, Linda J W, Schipper, Luuk J, Roepman, Paul, de Bruijn, Ewart, Hoes, Louisa R, Riethorst, Immy, Schoenmaker, Lieke, van der Kolk, Lizet E, Retèl, Valesca P, Frederix, Geert W J, Buffart, Tineke E, van der Hoeven, Jacobus J M, Voest, Emile E, Cuppen, Edwin, Monkhorst, Kim, and Meijer, Gerrit A

Published
2020

182. Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine

Author

CMM Sectie Molecular Cancer Research, Child Health, Regenerative Medicine and Stem Cells, Cancer, Hubrecht Institute with UMC, CMM, CMM Groep Cuppen, Dijkstra, Krijn K, Monkhorst, Kim, Schipper, Luuk J, Hartemink, Koen J, Smit, Egbert F, Kaing, Sovann, de Groot, Rosa, Wolkers, Monika C, Clevers, Hans, Cuppen, Edwin, Voest, Emile E, CMM Sectie Molecular Cancer Research, Child Health, Regenerative Medicine and Stem Cells, Cancer, Hubrecht Institute with UMC, CMM, CMM Groep Cuppen, Dijkstra, Krijn K, Monkhorst, Kim, Schipper, Luuk J, Hartemink, Koen J, Smit, Egbert F, Kaing, Sovann, de Groot, Rosa, Wolkers, Monika C, Clevers, Hans, Cuppen, Edwin, and Voest, Emile E

Published
2020

183. Tumor organoid–T-cell coculture systems

Author

Hubrecht Institute with UMC, Cattaneo, Chiara M., Dijkstra, Krijn K., Fanchi, Lorenzo F., Kelderman, Sander, Kaing, Sovann, van Rooij, Nienke, van den Brink, Stieneke, Schumacher, Ton N., Voest, Emile E., Hubrecht Institute with UMC, Cattaneo, Chiara M., Dijkstra, Krijn K., Fanchi, Lorenzo F., Kelderman, Sander, Kaing, Sovann, van Rooij, Nienke, van den Brink, Stieneke, Schumacher, Ton N., and Voest, Emile E.

Published
2020

188. Study protocol: Whole genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE)

Author

Samsom, Kris G., primary, Bosch, Linda J. W., additional, Schipper, Luuk J., additional, Roepman, Paul, additional, de Bruijn, Ewart, additional, Hoes, Louisa R., additional, Riethorst, Immy, additional, Schoenmaker, Lieke, additional, van der Kolk, Lizet E., additional, Retèl, Valesca P., additional, Frederix, Geert W. J., additional, Buffart, Tineke E., additional, van der Hoeven, Jacobus J. M., additional, Voest, Emile E., additional, Cuppen, Edwin, additional, Monkhorst, Kim, additional, and Meijer, Gerrit A., additional

Published
2020
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196. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer

Author

Rodenhuis, Sjoerd, Bontenbal, Marijke, Beex, Louk V.A.M., Wagstaff, John, Richel, Dick J., Nooij, Marianne A., Voest, Emile E., Hupperets, Pierre, Tinteren, Harm van, Peterse, Hans L., TenVergert, Elisabeth M., and Vries, Elisabeth G.E. de

Subjects
Breast cancer -- Care and treatment, Chemotherapy -- Dosage and administration
Abstract

High-dose chemotherapy and a blood stem cell transplant may benefit some women with breast cancer that has spread to four or more lymph nodes, according to a study of 885 women. Women with cancer in four or more lymph nodes have the highest rates of relapse after traditional chemotherapy. Women who receive high-dose chemotherapy also receive a blood stem cell transplant because the chemotherapy damages their immune system.

Published
2003

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