scholarly journals Unsymmetric Cisplatin-Based Pt(IV) Conjugates Containing a PARP-1 Inhibitor Pharmacophore Tested on Malignant Pleural Mesothelioma Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4740
Author(s):  
Elisabetta Gabano ◽  
Giulia Pinton ◽  
Cecilia Balzano ◽  
Sara Boumya ◽  
Domenico Osella ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Chemotherapeutic Agent ◽  
Acquired Resistance ◽  
Platinum Drugs ◽  
Pleural Mesothelioma ◽  
Wild Type ◽  
Multicellular Spheroids ◽  
First Line ◽  
Malignant Pleural Mesothelioma Cell ◽  
Parp 1

Cisplatin is widely employed as a first-line chemotherapeutic agent for many solid tumors, including malignant pleural mesothelioma (MPM). However, its clinical use is limited by heavy side effects and acquired resistance, the latter being mainly related to enhanced DNA repair. Many clinical trials using combinations of platinum drugs and PARP-1 inhibitors (PARPis) have been carried out, with the hope that such combinations might lead to improved therapeutic efficacy against tumors. Here, the synthesis and efficacy in reducing MPM cell viability of four cisplatin-based Pt(IV) prodrugs containing the PARPi 3-aminobenzamide (3-ABA) fragment are described. The most promising conjugate is more effective than cisplatin or cisplatin/3-ABA combination, administered in equimolar doses, in inhibiting PARP-1 activity and inducing apoptosis in BRCA1/2 wild type MPM cells, grown as monolayer or as multicellular spheroids.

scholarly journals Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments

Thorax ◽  
2020 ◽  
Vol 75 (11) ◽  
pp. 1004-1008 ◽  
Author(s):  
Nikolaos I Kanellakis ◽  
Rachelle Asciak ◽  
Megat Abd Hamid ◽  
Xuan Yao ◽  
Mark McCole ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Ex Vivo ◽  
Cytotoxic T Cells ◽  
Pleural Mesothelioma ◽  
Ex Vivo Model ◽  
High Throughput Drug Screening ◽  
Aggressive Cancer ◽  
Malignant Pleural Mesothelioma Cell

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

scholarly journals Rechallenge for Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan

JAMA Oncology ◽  
2019 ◽  
Vol 5 (3) ◽  
pp. 343 ◽  
Author(s):  
Chiara Cremolini ◽  
Daniele Rossini ◽  
Emanuela Dell’Aquila ◽  
Sara Lonardi ◽  
Elena Conca ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Acquired Resistance ◽  
Wild Type ◽  
First Line

Outcomes with first-line platinum-based combination chemotherapy for malignant pleural mesothelioma: A review of practice in British Columbia

Lung Cancer ◽  
2009 ◽  
Vol 64 (3) ◽  
pp. 308-313 ◽  
Author(s):  
Christopher W. Lee ◽  
Nevin Murray ◽  
Helen Anderson ◽  
Sanjay C. Rao ◽  
Winston Bishop
Keyword(s):  
British Columbia ◽  
Malignant Pleural Mesothelioma ◽  
Combination Chemotherapy ◽  
Pleural Mesothelioma ◽  
First Line
Sign in / Sign up

Export Citation Format

Share Document