The protein can predict the results of targeted therapy mccRCC -
By Sarah Pritchard, medwireNews Reporter
The levels of carbonic anhydrase 9 (CA9) increase with use vascular endothelial growth factor (VEGF) -targeted therapy for metastatic clear cell renal cell carcinoma (mccRCC) and high expression of this protein is associated with increased survival, the results show study published in European Urology .
researchers found "consistent dynamic changes to CA9 chromosomal and protein levels" and suggests the results may have an interest in mccRCC patients with tumors refractory to sunitinib.
" CA9 modulation to overcome the resistance of the anti-VEGF therapy may be a potential therapeutic area investigated in the future, "write Thomas Powles (Queen Mary University of London, UK) and colleagues.
results could also help answer some current molecular methods, validated improving the prognosis or predicting response to targeted therapies mccRCC patients, they add.
team assessed the presence of 55 proteins known to be relevant in the RCC pathogenesis or sunitinib response in tumor tissues of 22 and 23 mccRCC naive sunitinib sunitinib-treated patients
in all, 30 of the 55 proteins were differentially expressed in treated and untreated patients, with four in particular showing intratumoral increased variance after sunitinib. CA9, CLL B / cell lymphoma 2 mutL homolog 1 and mTOR.
After further evaluation of these proteins in tumor samples matched treated and untreated from a separate cohort validation (n = 86), only CA9 was significantly increased in the treated tissues. Indeed, a strong expression of CA9 was associated with improved overall survival, reducing the risk of death from mccRCC by a significant 74%, reports the research team.
Multivariate analysis adjusted for potentially confounding prognostic factors revealed that a low Fuhrman grade and CA9 highest expression in tissue samples nephrectomy were associated with significantly improved overall survival (ratios risk = 0.51 and 0.48, respectively).
Powles and his colleagues also performed a functional analysis of CA9 in theCAKI-2 and RCC11 lines of kidney cancer cells and found that CA9 shut interference blocked RNA anti-proliferative effects of sunitinib .
"These results confirm the findings of clinical tissue, where low levels of CA9 was associated with poor prognosis of sunitinib therapy," the researchers write
Powles et al continue :. "The work presented here shows that not only targeted therapy to increase expression of CA9, but these changing levels are also prognostic." This raises the possibility of a biomarker prediction in this context.
"a randomized trial comparing continued treatment with a change of treatment in patients who failed to achieve a level rise CA9 with therapy would test this prospective biomarker" concluent- they.
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