Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation
Maria Natalia Gandur Quiroga shared on X:
“Key Findings from the Study on Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation:
Niraparib’s Unique Interaction:
Distinct Target: Niraparib binds to lanosterol synthase (LSS), not seen with other PARP inhibitors.
Pathway Activation: Triggers the 24,25-epoxysterol shunt pathway, regulating cholesterol biosynthesis.
Enhanced Cancer Cell Killing:
Combination Therapy: LSS inhibitors with PARP inhibitors like olaparib show additive effects.
Synergy with Statins: Combining PARP inhibitors with statins leads to stronger tumor cell killing.
Mechanistic Insights:
Metabolite Analysis: Increased levels of 24,25-epoxycholesterol and other intermediates with niraparib.
Thermal Proteome Profiling: Niraparib stabilizes LSS, indicating a direct interaction.
Clinical Implications:
Improved Efficacy: Potential for better treatment outcomes in cholesterol-dependent tumors.
Further Research Needed: More studies required to confirm clinical relevance. ”
‘Synergistic effects of PARP inhibition and cholesterol biosynthesis pathway modulation‘
Authors: Anna Rutkowska, H. Christian Eberl, Thilo Werner, Marco L. Hennrich, Daniel C. Sévin, Massimo Petretich, James P. Reddington, Shirin Pocha, Stephan Gade, Amalia Martinez-Segura, Dmytro Dvornikov, Joel Karpiak, Gavain M.A. Sweetman, Christian Fufezan, Birgit Duempelfeld, Florian Braun, Christopher Schofield, Hakan Keles, David Alvarado, Zhuo Wang, Keith H. Jansson, Maria Faelth-Savitski, Edward Curry, Katja Remlinger, Euan A Stronach, Bin Feng, Geeta Sharma, Kevin Coleman, Paola Grandi, Marcus Bantscheff, Giovanna Bergamini.
Source: Maria Natalia Gandur Quiroga/X
Maria Natalia Gandur Quiroga is a Medical Oncologist and Chief of the Division of Genitourinary Medical Oncology at the Instituto de Oncología Ángel H. Roffo in Buenos Aires, Argentina. She is a Professor of Medicine at the University of Buenos Aires at the Oncologists Post Graduates Studies.
Her research focuses on clinical trials with aims to improve the treatment of patients with urologic tumors. She is an active member of the European Association for Cancer Research, Argentinian Medical Association and American Society of Clinical Oncology.
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