Article
Pharmacology & Pharmacy
Giovanni Canil, Marco Orleni, Bianca Posocco, Sara Gagno, Alessia Bignucolo, Marcella Montico, Rossana Roncato, Serena Corsetti, Michele Bartoletti, Giuseppe Toffoli
Summary: Poly (ADP-ribose) polymerase inhibitors (PARPis) are increasingly important in oncology, and their therapeutic drug monitoring (TDM) could benefit patients. This study developed and validated a liquid chromatography-tandem mass spectrometry method for quantifying olaparib, rucaparib, and niraparib in both human plasma and dried blood spot (DBS). The correlation between drug concentrations measured in these two matrices was assessed. Results showed a strong correlation between plasma and DBS for olaparib and niraparib, though further data is needed to establish a robust regression analysis for rucaparib. The study provides a solid foundation for the feasibility of using both plasma and DBS matrices for PARPis TDM.
Article
Oncology
Pierre Loap, Delphine Loirat, Frederique Berger, Manuel Rodrigues, Louis Bazire, Jean-Yves Pierga, Anne Vincent-Salomon, Fatima Laki, Latifa Boudali, Laurence Raizonville, Veronique Mosseri, Anne Jochem, Alexandre Eeckhoutte, Mamadou Diallo, Marc-Henri Stern, Alain Fourquet, Youlia Kirova
Summary: This study aimed to assess the safety and tolerability of combining olaparib with radiotherapy in TNBC patients. The results showed that this combination therapy was well tolerated in patients with early-stage, high-risk TNBC and should continue to be evaluated in further clinical trials.
Article
Oncology
Shannon N. Westin, Marilyne Labrie, Jennifer K. Litton, Aurora Blucher, Yong Fang, Christopher P. Vellano, Joseph R. Marszalek, Ningping Feng, XiaoYan Ma, Allison Creason, Bryan Fellman, Ying Yuan, Sanghoon Lee, Tae-Beom Kim, Jinsong Liu, Anca Chelariu-Raicu, Tsun Hsuan Chen, Nashwa Kabil, Pamela T. Soliman, Michael Frumovitz, Katheleen M. Schmeler, Amir Jazaeri, Karen H. Lu, Rashmi Murthy, Larissa A. Meyer, Charlotte C. Sun, Anil K. Sood, Robert L. Coleman, Gordon B. Mills
Summary: This study aimed to confirm the recommended phase II dose for the combination of olaparib and capivasertib in multiple cancers, and evaluate molecular markers of response and resistance. Promising responses, especially in endometrial cancer, were observed among the 38 enrolled patients. Therapy resistance was associated with specific signaling pathways and metabolic factors.
CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Sayeh Saravi, Zena Alizzi, Sabrina Tosi, Marcia Hall, Emmanouil Karteris
Summary: This study aimed to assess the effects of the PARPi rucaparib in vitro on cell lines with BRCA2 mutations, revealing significant impact on DNA damage and the mTOR pathway of PEO1 cells.
Article
Medicine, Research & Experimental
Jinyu Meng, Jin Peng, Jie Feng, Jochen Maurer, Xiao Li, Yan Li, Shu Yao, Ran Chu, Xiyu Pan, Junting Li, Ting Zhang, Lu Liu, Qing Zhang, Zeng Yuan, Hualei Bu, Kun Song, Beihua Kong
Summary: Niraparib modulates the immune response through activation of the cGAS/STING pathway and in combination with PD-L1 blockade can further enhance the effect.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Pierre Loap, Delphine Loirat, Frederique Berger, Francesco Ricci, Anne Vincent-Salomon, Cyrine Ezzili, Veronique Mosseri, Alain Fourquet, Monia Ezzalfani, Youlia Kirova
Summary: Preclinical studies have shown that TNBC cell lines are more sensitive to PARP inhibitors, leading to the development of new therapeutic approaches. The RADIOPARP phase 1 trial aimed to evaluate the toxicity and maximum tolerated dose of olaparib in combination with radiation therapy for TNBC patients. The trial showed that olaparib at a dose of 200 mg twice a day was well tolerated without dose-limiting toxicities.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2021)
Review
Oncology
Jing Luo, Shunlong Ou, Hua Wei, Xiaoli Qin, Qian Jiang
Summary: This study compared the efficacy and safety of different PARP inhibitors in ovarian cancer patients through a network meta-analysis. The results showed that there is no significant difference in efficacy among olaparib, niraparib, and rucaparib, but olaparib may have fewer adverse events.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
F. Guffanti, M. F. Alvisi, A. Anastasia, F. Ricci, M. Chiappa, A. Llop-Guevara, V Serra, R. Fruscio, A. Degasperi, S. Nik-Zainal, M. R. Bani, M. Lupia, R. Giavazzi, E. Rulli, G. Damia
Summary: This study demonstrates that the RAD51 foci score can predict the response to olaparib in ovarian cancer patients, providing a simple and feasible biomarker for clinical application. Furthermore, the findings emphasize the importance of ovarian cancer patient-derived xenografts (PDXs) as a reliable tool for identifying and validating biomarkers of response to therapy.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Kathryn M. Appleton, Ashley K. Elrod, Katy A. Lassahn, Stephen Shuford, Lillia M. Holmes, Teresa M. DesRochers
Summary: This study examined the effectiveness of using three-dimensional (3D) spheroids to detect patient-specific immune-related activity in ovarian cancer. It found that some patients had higher sensitivity to immune checkpoint inhibitors and demonstrated increases in cytotoxic T cell activation and DC major histocompatibility complex (MHC) class-II expression upon cytokine stimulation. Ex vivo 3D spheroid platforms accurately detected immune cell activity and modulation, providing evidence for their utility in showing sensitivity to ICIs alone or in combination with PARP-Is in a preclinical setting.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Alfonso Yubero, Aranzazu Barquin, Purificacion Estevez, Bella Pajares, Luisa Sanchez, Piedad Reche, Jesus Alarcon, Julia Calzas, Lydia Gaba, Jose Fuentes, Ana Santaballa, Carmen Salvador, Luis Manso, Ana Herrero, Alvaro Taus, Raul Marquez, Julia Madani, Maria Merino, Gloria Marquina, Victoria Casado, Manuel Constenla, Maria Gutierrez, Alba Dosil, Antonio Gonzalez-Martin
Summary: This study analyzed the efficacy and safety of rucaparib in the treatment of ovarian cancer within the RAP in Spain. The results showed that the efficacy of rucaparib in maintenance therapy and treatment was similar to previous trials, and the safety profile in real life was predictable and manageable.
Article
Biotechnology & Applied Microbiology
Jingyan Yi, Xin Luo, Jinshan Xing, Aharon Gedanken, Xiukun Lin, Chunxiang Zhang, Gan Qiao
Summary: The anticancer effects of MEnZn-CuO NPs on human ovarian cancer cells were studied, and it was found that they could affect cell proliferation, migration, apoptosis, and autophagy. In addition, MEnZn-CuO NPs have a greater potential for clinical application by inducing HR repair defects in ovarian cancer cells in combination with poly (ADP-ribose) polymerase inhibitors for lethal effects.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Shaily Arora, Sanjeeve Balasubramaniam, Hui Zhang, Tara Berman, Preeti Narayan, Daniel Suzman, Erik Bloomquist, Shenghui Tang, Yutao Gong, Rajeshwari Sridhara, Francisca Reyes Turcu, Deb Chatterjee, Banu Saritas-Yildirim, Soma Ghosh, Reena Philip, Anand Pathak, Jennifer J. Gao, Laleh Amiri-Kordestani, Richard Pazdur, Julia A. Beaver
Summary: FDA approved olaparib monotherapy and combination therapy with bevacizumab for the first-line treatment of advanced ovarian cancer with BRCA mutations and homologous recombination deficient-positive status. Both treatments demonstrated clinically meaningful improvements in progression-free survival and favorable benefit-risk profiles in clinical trials.
Review
Pharmacology & Pharmacy
Luigi Della Corte, Virginia Foreste, Claudia Di Filippo, Pierluigi Giampaolino, Giuseppe Bifulco
Summary: PARP inhibitors, targeting the loss of gene suppressor, block base-excision repair in cancer cells with BRCA mutations, leading to synthetic lethality and cell death, potentially playing a crucial role in personalized therapeutic programs for EOC treatment.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
Article
Oncology
Alan P. Lombard, Cameron M. Armstrong, Leandro S. D'Abronzo, Shu Ning, Amy R. Leslie, Masuda Sharifi, Wei Lou, Christopher P. Evans, Marc Dall'Era, Hong-Wu Chen, Xinbin Chen, Allen C. Gao
Summary: PARP inhibition represents the dawn of precision medicine for treating prostate cancer. This study investigates how PARP inhibitor-sensitive tumor cells respond to treatment and how resistance to PARP inhibitors develops. The research team characterized the response to olaparib in sensitive cells and developed olaparib-resistant cells to study resistance mechanisms. They found that olaparib induces DNA damage, activates the G(2)-M checkpoint, and leads to cell-cycle arrest in sensitive cells. In contrast, olaparib-resistant cells do not arrest at G(2)-M and display a blunted response to olaparib treatment. The study provides insights into PARP inhibitor treatment and offers a cellular platform system for studying response and resistance to PARP inhibition.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Chemistry, Organic
Zijun Chen, Gianluca Destro, Florian Guibbal, Chung Ying Chan, Bart Cornelissen, Veronique Gouverneur
Summary: This study presents two strategies for accessing the F-18-isotopologue of rucaparib using a copper-mediated nucleophilic F-18-fluorodeboronation. The most successful approach involves an aldehydic boronic ester precursor and reductive amination post-F-18-labeling, resulting in [F-18]rucaparib with a high activity yield and molar activity. Preliminary in vitro studies showed promising results.