E-resources
Peer reviewed
Open access
-
Rushing, Blake R
Biomedicines, 09/2023, Volume: 11, Issue: 9Journal Article
Drug resistance continues to be a significant problem in cancer therapy, leading to relapse and associated mortality. Although substantial progress has been made in understanding drug resistance, significant knowledge gaps remain concerning the molecular underpinnings that drive drug resistance and which processes are unique to certain drug classes. The NCI-60 cell line panel program has evaluated the activity of numerous anticancer agents against many common cancer cell line models and represents a highly valuable resource to study intrinsic drug resistance. Furthermore, great efforts have been undertaken to collect high-quality omics datasets to characterize these cell lines. The current study takes these two sources of data—drug response and omics profiles—and uses a multi-omics investigation to uncover molecular networks that differentiate cancer cells that are sensitive or resistant to antifolates, which is a commonly used class of anticancer drugs. Results from a combination of univariate and multivariate analyses showed numerous metabolic processes that differentiate sensitive and resistant cells, including differences in glycolysis and gluconeogenesis, arginine and proline metabolism, beta-alanine metabolism, purine metabolism, and pyrimidine metabolism. Further analysis using multivariate and integrated pathway analysis indicated purine metabolism as the major metabolic process separating cancer cells sensitive or resistant to antifolates. Additional pathways differentiating sensitive and resistant cells included autophagy-related processes (e.g., phagosome, lysosome, autophagy, mitophagy) and adhesion/cytoskeleton-related pathways (e.g., focal adhesion, regulation of actin cytoskeleton, tight junction). Volcano plot analysis and the receiver operating characteristic (ROC) curves of top selected variables differentiating Q1 and Q4 revealed the importance of genes involved in the regulation of the cytoskeleton and extracellular matrix (ECM). These results provide novel insights toward mechanisms of intrinsic antifolate resistance as it relates to interactions between nucleotide metabolism, autophagy, and the cytoskeleton. These processes should be evaluated in future studies to potentially derive novel therapeutic strategies and personalized treatment approaches to improve antifolate response.
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.