scholarly journals Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma

2016 ◽  
Vol 16 (1) ◽  
pp. 76-87 ◽  
Author(s):  
Amro Aboukameel ◽  
Irfana Muqbil ◽  
William Senapedis ◽  
Erkan Baloglu ◽  
Yosef Landesman ◽  
...  
2006 ◽  
Vol 66 (21) ◽  
pp. 10525-10533 ◽  
Author(s):  
Amit Verma ◽  
Huamin Wang ◽  
Bramanandam Manavathi ◽  
Jansina Y. Fok ◽  
Aman P. Mann ◽  
...  

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Jiali Du ◽  
Jichun Gu ◽  
Ji Li

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide, and the mortality of patients with PDAC has not significantly decreased over the last few decades. Novel strategies exhibiting promising effects in preclinical or phase I/II clinical trials are often situated in an embarrassing condition owing to the disappointing results in phase III trials. The efficacy of the current therapeutic regimens is consistently compromised by the mechanisms of drug resistance at different levels, distinctly more intractable than several other solid tumours. In this review, the main mechanisms of drug resistance clinicians and investigators are dealing with during the exploitation and exploration of the anti-tumour effects of drugs in PDAC treatment are summarized. Corresponding measures to overcome these limitations are also discussed.


2021 ◽  
Author(s):  
Solange Le Blanc ◽  
Naveed Ishaque ◽  
Julia Jabs ◽  
Tobias Bauer ◽  
Sebastian Schuth ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is characterized by high drug resistance and poor prognosis. Novel therapeutic and stratification strategies are urgently needed. Here, we present an integration of in-depth genomic and transcriptomic characterization with drug screening and clinical outcome based on a catalogue of 51 patient-derived tumor organoids (PDOs) from resected PDAC. Known PDAC molecular subtypes and their prognostic value are conserved in organoids. Integration of transcriptomic and drug response profiles suggest a metabolism-mediated modulations of drug resistance. Copy number alterations on chromosome 13q and wild-type status of TP53 emerged as potential novel genomic biomarkers for sensitivity to 5-FU and oxaliplatin treatment, respectively. Functional testing of targeted drugs in PDOs revealed its additional value for genome-driven personalized oncology. Co-deletion of TP53/POLR2A increased vulnerability to RNA polymerase II inhibition, pointing to a promising target for personalized treatment in PDAC.


2015 ◽  
Author(s):  
Elisa M. Noll ◽  
Christian Eisen ◽  
Elisa Espinet ◽  
Vanessa Vogel ◽  
Corinna Klein ◽  
...  

2013 ◽  
Vol 333 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Min Xu ◽  
Lei Li ◽  
Zhiqiang Liu ◽  
Zhijun Jiao ◽  
Ping Xu ◽  
...  

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