Is blocking of NF-kB activation in metastatic early breast cancer an effective therapeutic approach?
|Year of publication||2016|
|Description||Current prognostic factors are insufficient for precise risk-discrimination in breast cancer patients with low grade breast tumors, which, in disagreement with theoretical prognosis, occasionally form early lymph node metastases. To identify and clinically validate potential markers associated with a metastatic potential of these tumors, we performed a combined proteomics and transcriptomics study on lymph node positive vs. negative grade 1 luminal A primary breast tumors. Tumors of another breast cancer subtypes were also analyzed to investigate marker specificity. Within the panel of top 10 proteins upregulated in metastatic primary low-grade tumors, there are several NF ?B associated proteins: p63/RELA, RNF25, TRAF3IP2 and PDLIM2. Hence, NF ?B targeting could be hypothesized as an anti-metastatic therapeutic strategy for this subtype. Interestingly, the results from the phase III ABCSG-18 clinical trial showed that the use of receptor activator of nuclear factor-kappa B ligand (RANKL) inhibitor denosumab improves disease-free survival for postmenopausal patients with hormone receptor positive breast cancer and should be used in combination with aromatase inhibitors. Although the data is still insufficient in term of anti-metastatic effect, it indicates that NF-?B modulation could be an effective approach in early breast cancer treatment. This work was supported by Czech Science Foundation (project No. 14-19250S), by the project MEYS – NPS I – LO1413 and by MH CZ - DRO (MMCI, 00209805).|