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5 results on '"Baiden-Amissah, Regina"'

1. Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers

Author

Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, Amant, Frédéric, Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, and Amant, Frédéric

Abstract

Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12–15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the lack of clinical applicability limits exploitation of many potential targets, leaving patients with limited options. Serine biosynthesis has been linked to cancer growth and poor prognosis in various cancer types, however its role in platinum-resistant ovarian cancer is not known. Here, we show that a subgroup of resistant tumors decreases phosphoglycerate dehydrogenase (PHGDH) expression at relapse after platinum-based chemotherapy. Mechanistically, we observe that this phenomenon is accompanied by a specific oxidized nicotinamide adenine dinucleotide (NAD+) regenerating phenotype, which helps tumor cells in sustaining Poly (ADP-ribose) polymerase (PARP) activity under platinum treatment. Our findings reveal metabolic vulnerabilities with clinical implications for a subset of platinum resistant ovarian cancers.

Published
2022

2. Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers

Author

Veterinaire biochemie, Faculteit Diergeneeskunde, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, Amant, Frédéric, Veterinaire biochemie, Faculteit Diergeneeskunde, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, and Amant, Frédéric

Published
2022

3. Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers

Author

Veterinaire biochemie, Faculteit Diergeneeskunde, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, Amant, Frédéric, Veterinaire biochemie, Faculteit Diergeneeskunde, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, and Amant, Frédéric

Published
2022

4. Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers

Author

Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, Amant, Frédéric, Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, and Amant, Frédéric

Abstract

Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12–15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the lack of clinical applicability limits exploitation of many potential targets, leaving patients with limited options. Serine biosynthesis has been linked to cancer growth and poor prognosis in various cancer types, however its role in platinum-resistant ovarian cancer is not known. Here, we show that a subgroup of resistant tumors decreases phosphoglycerate dehydrogenase (PHGDH) expression at relapse after platinum-based chemotherapy. Mechanistically, we observe that this phenomenon is accompanied by a specific oxidized nicotinamide adenine dinucleotide (NAD+) regenerating phenotype, which helps tumor cells in sustaining Poly (ADP-ribose) polymerase (PARP) activity under platinum treatment. Our findings reveal metabolic vulnerabilities with clinical implications for a subset of platinum resistant ovarian cancers.

Published
2022

5. Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study

Author

De Jaeghere, Emiel, Tuyaerts, Sandra, Van Nuffel, An M T, Belmans, Ann, Bogaerts, Kris, Baiden-Amissah, Regina, Lippens, Lien, Vuylsteke, Peter, Henry, Stéphanie, Trinh, Xuan Bich, Van Dam, Peter P.A., Aspeslagh, Sandrine, De Caluwé, Alex, Naert, Eline, Lambrechts, Diether, Hendrix, An, De Wever, Olivier, Van de Vijver, Koen, Amant, Frédéric, Vandecasteele, Katrien, Denys, Hannelore, De Jaeghere, Emiel, Tuyaerts, Sandra, Van Nuffel, An M T, Belmans, Ann, Bogaerts, Kris, Baiden-Amissah, Regina, Lippens, Lien, Vuylsteke, Peter, Henry, Stéphanie, Trinh, Xuan Bich, Van Dam, Peter P.A., Aspeslagh, Sandrine, De Caluwé, Alex, Naert, Eline, Lambrechts, Diether, Hendrix, An, De Wever, Olivier, Van de Vijver, Koen, Amant, Frédéric, Vandecasteele, Katrien, and Denys, Hannelore

Abstract

A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0–31.0) in cervical cancer and 12.0% (90% CI 3.4–28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1–25.7) in cervical cancer and 3.6 weeks (95% CI 3.6–15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0–67.0) and 37.4 weeks (95% CI 19.0–50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity. Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97)., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2022

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