Chemoresistance mechanisms of colorectal cancer remain largely elusive. We aim to compare the difference of chemotherapy responses between FOLFOX-resistant and wild-type colorectal cancer cells by proteomic profiling to suggest novel treatment targets. FOLFOX-resistant colorectal cancer cells DLD1-R and HCT116-R were developed by chronic exposure to progressive FOLFOX doses. Proteomic profiling of FOLFOX-resistant and wild-type cells under FOLFOX exposure were conducted by mass-spectrometry-based protein-analysis technology. Verification of selected KEGG pathways was conducted by Western blot. DLD1-R had significantly higher FOLFOX-chemoresistance (10.81 times) than its wild-type counterpart. A total of 309 and 90 differentially expressed proteins were identified in DLD1-R and HCT116-R, respectively. In terms of gene ontology molecular function, RNA binding and cadherin binding ranked first for DLD1 and HCT116 groups, respectively. For gene set enrichment analysis, ribosome pathway and DNA replication were significantly up-regulated and down-regulated in DLD1-R, respectively. The most significantly up-regulated pathway in HCT116-R was regulation of the actin cytoskeleton. Up-regulations in the ribosome pathway (DLD1-R) and actin cytoskeleton (HCT116-R) were verified by Western blot. There were several significantly altered signaling pathways in FOLFOX-resistant colorectal cancer cells under FOLFOX with notable up-regulations in the ribosomal process and actin cytoskeleton.

A previous study investigated robustness of manual flash (MF) and robust optimized (RO) volumetric modulated arc therapy plans for breast radiotherapy based on five patients in 2020 and indicated that the RO was more robust than the MF, although the MF is still current standard practice. The purpose of this study was to compare their plan robustness in terms of dose variation to clinical target volume (CTV) and organs at risk (OARs) based on a larger sample size. This was a retrospective study involving 34 female patients. Their plan robustness was evaluated based on measured volume/dose difference between nominal and worst scenarios (ΔV/ΔD) for each CTV and OARs parameter, with a smaller difference representing greater robustness. Paired sample t-test was used to compare their robustness values. All parameters (except CTV ΔD_98%) of the RO approach had smaller ΔV/ΔD values than those of the MF. Also, the RO approach had statistically significantly smaller ΔV/ΔD values (p < 0.001–0.012) for all CTV parameters except the CTV ΔV_95% and ΔD_98% and heart ΔD_mean. This study’s results confirm that the RO approach was more robust than the MF in general. Although both techniques were able to generate clinically acceptable plans for breast radiotherapy, the RO could potentially improve workflow efficiency due to its simpler planning process.