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. 2010 Jun 8;5(6):e11013. doi: 10.1371/journal.pone.0011013

Figure 4. Rapamycin therapy inhibits tumoral and PBMC downstream targets of mTOR in a clinical setting.

Figure 4

Modulation of mTOR pathway targets were evaluated in matched tumor (A.) and PBMC samples (B.) to compare pS6RP pre- and post-rapamycin therapy. Electrochemiluminescence (ECL) was utilized to accurately quantify phospho-protein status in tumor and PBMC. Quality control assessments defined 10 tumor and 8 PBMC samples eligible for evaluation. A. The red bars below the x-axis indicate patient dosing cohorts. Pre-treatment bars (purple) represent p-S6RP tumor levels prior to rapamycin dosing and post-treatment bars (blue) represent Day 8 levels at tumor surgical excision. Rapamycin led to >2-fold inhibition of tumoral p-S6RP in 8/10 dogs (A, p<0.0001). B. PBMC phosphorylation of S6RP was significantly inhibited in 8/8 dogs evaluated at Day 8 after rapamycin therapy and was maintained through Day 15 (7 days after the cessation of rapamycin therapy) (B, p<0.0001). Matched PBMC and tumor sample data were concordant. Marked post-treatment mTOR pathway inhibition was seen in dogs from all dose cohorts, including the lowest dose cohorts (0.01–0.02 mg/kg), proving that p-S6RP is a very sensitive biomarker of rapamycin administration.