scholarly journals Genetic load makes cancer cells more sensitive to common drugs: evidence from Cancer Cell Line Encyclopedia

2017 ◽  
Author(s):  
Ana B. Pavel ◽  
Kirill S. Korolev
Keyword(s):  
Cell Line ◽  
Anticancer Drugs ◽  
Cancer Cell ◽  
Genetic Load ◽  
Cancer Cell Line ◽  
Genetic Alterations ◽  
Cell Cycle Checkpoints ◽  
Tissue Type ◽  
Cancer Cell Line Encyclopedia ◽  
Negative Effect

AbstractGenetic alterations initiate tumors and enable the evolution of drug resistance. The pro-cancer view of mutations is however incomplete, and several studies show that mutational load can reduce tumor fitness. Given its negative effect, genetic load should make tumors more sensitive to anticancer drugs. Here, we test this hypothesis across all major types of cancer from the Cancer Cell Line Encyclopedia, that provides genetic and expression data of 496 cell lines together with their response to 24 common anticancer drugs. We found that the efficacy of 9 out of 24 drugs showed significant association with genetic load in a pan-cancer analysis. The associations for some tissue-drug combinations were remarkably strong with genetic load explaining up to 83% of the variance in the drug response. Overall, the role of genetic load depended on both the drug and the tissue type with 10 tissues being particularly vulnerable to genetic load. We also identified changes in gene expression associated with increased genetic load, which included cell-cycle checkpoints, DNA damage and apoptosis. Our results show that genetic load is an important component of tumor fitness and can predict drug sensitivity. Beyond being a biomarker, genetic load might be a new, unexplored vulnerability of cancer.

scholarly journals Establishment and Characterization of a Novel Multidrug Resistant Human Ovarian Cancer Cell Line With Heterogenous MRP7 Overexpression

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing-Quan Wang ◽  
Zhuo-Xun Wu ◽  
Yuqi Yang ◽  
Jin-Sui Li ◽  
Dong-Hua Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Multidrug Resistance ◽  
Cell Line ◽  
Anticancer Drugs ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Chemotherapeutic Drugs ◽  
Mesenchymal Transition

Ovarian cancer is one of the leading female malignancies which accounts for the highest mortality rate among gynecologic cancers. Surgical cytoreduction followed by chemotherapy is the mainstay of treatment. However, patients with recurrent ovarian cancer are likely to exhibit resistance to chemotherapy due to reduced sensitivity to chemotherapeutic drugs. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been extensively studied as multidrug resistance (MDR) mediators since they are responsible for the efflux of various anticancer drugs. Multidrug resistance protein 7 (MRP7, or ABCC10) was discovered in 2001 and revealed to transport chemotherapeutic drugs. Till now, only limited knowledge was obtained regarding its roles in ovarian cancer. In this study, we established an MRP7-overexpressing ovarian cancer cell line SKOV3/MRP7 via transfecting recombinant MRP7 plasmids. The SKOV3/MRP7 cell line was resistant to multiple anticancer drugs including paclitaxel, docetaxel, vincristine and vinorelbine with a maximum of 8-fold resistance. Biological function of MRP7 protein was further determined by efflux-accumulation assays. Additionally, MTT results showed that the drug resistance of the SKOV3/MRP7 cells was reversed by cepharanthine, a known inhibitor of MRP7. Moreover, we also found that the overexpression of MRP7 enhanced the migration and epithelial-mesenchymal transition (EMT) induction. In conclusion, we established an in vitro model of MDR in ovarian cancer and suggested MRP7 overexpression as the leading mechanism of chemoresistance in this cell line. Our results demonstrated the potential relationship between MRP7 and ovarian cancer MDR.

scholarly journals Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3712
Author(s):  
Paola Peinado ◽  
Alvaro Andrades ◽  
Marta Cuadros ◽  
Maria Isabel Rodriguez ◽  
Isabel F. Coira ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Genetic Alterations ◽  
Cell Models ◽  
Functional Studies ◽  
Cellular Models ◽  
Mutational Status

Mammalian SWI/SNF (SWitch/Sucrose Non-Fermentable) complexes are ATP-dependent chromatin remodelers whose subunits have emerged among the most frequently mutated genes in cancer. Studying SWI/SNF function in cancer cell line models has unveiled vulnerabilities in SWI/SNF-mutant tumors that can lead to the discovery of new therapeutic drugs. However, choosing an appropriate cancer cell line model for SWI/SNF functional studies can be challenging because SWI/SNF subunits are frequently altered in cancer by various mechanisms, including genetic alterations and post-transcriptional mechanisms. In this work, we combined genomic, transcriptomic, and proteomic approaches to study the mutational status and the expression levels of the SWI/SNF subunits in a panel of 38 lung adenocarcinoma (LUAD) cell lines. We found that the SWI/SNF complex was mutated in more than 76% of our LUAD cell lines and there was a high variability in the expression of the different SWI/SNF subunits. These results underline the importance of the SWI/SNF complex as a tumor suppressor in LUAD and the difficulties in defining altered and unaltered cell models for the SWI/SNF complex. These findings will assist researchers in choosing the most suitable cellular models for their studies of SWI/SNF to bring all of its potential to the development of novel therapeutic applications.

scholarly journals Tumor Suppressors Status in Cancer Cell Line Encyclopedia

2013 ◽  
Vol 7 (4) ◽  
pp. 791-798 ◽  
Author(s):  
Dmitriy Sonkin ◽  
Mehedi Hassan ◽  
Denis J. Murphy ◽  
Tatiana V. Tatarinova
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Tumor Suppressors ◽  
Cancer Cell Line ◽  
Cancer Cell Line Encyclopedia

Abstract PR4: Integrative analysis of genomic and pharmacologic data from the Cancer Cell Line Encyclopedia

2010 ◽  
Author(s):  
Nicolas Stransky ◽  
Kavitha Venkatesan ◽  
Jordi Barretina ◽  
Giordano Caponigro ◽  
Adam Margolin ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Integrative Analysis ◽  
Cancer Cell Line Encyclopedia

22 The Cancer Cell Line Encyclopedia - Using Preclinical Models to Predict Anticancer Drug Sensitivity

2012 ◽  
Vol 48 ◽  
pp. S5-S6 ◽  
Author(s):  
J. Barretina ◽  
G. Caponigro ◽  
N. Stransky ◽  
K. Venkatesan ◽  
A.A. Margolin ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Cancer Cell Line ◽  
Preclinical Models ◽  
Cancer Cell Line Encyclopedia
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