Abstract
Objective: Epidermal growth factor receptor inhibitors (EGFRI) are used as targeted cancer therapy. On average 70% of patients treated with EGFRIs suffer from skin toxicity. Studies showed a correlation between overall survival and the appearance of a skin rash, which is used as a biomarker for therapy efficacy. Micro RNAs (miRNA) as tumor or resistance biomarkers for cancer therapy are also highly investigated. In our study, we searched for associations of miRNA expression profiles in serum, with the severity of skin rash, in order to identify tentative therapy predictive biomarkers.Materials and Methods: Five candidate miRNAs were selected, based on an earlier in vitro next-generation-sequencing-experiment and after literature search. MiR-21, miR-31, miR-17, miR-106b and miR-520e were investigated in serum samples from patients (n = 254) treated with EGFRI. The quantitative expression of miRNA was tested for association with the occurrence/severity of the rash.Results: In our cohort of patients treated with EGFR inhibiting monoclonal antibodies, miR-21 and miR-520e serum concentrations were negatively correlated with severity of skin rash (p-value 0.000582 and 1.53e-07 linear-trend-test) whereas for miR-31, a positive correlation was observed (p-value 9.01e-06 linear-trend-test).Conclusions: This suggests that miR-21, miR-31 and miR-520e expression might be a treatment dependent marker for EGFRI induced skin rash.
Highlights
EGF receptor (EGFR)-InhibitorsEpidermal growth factor receptor inhibitors (EGFRI) belong to the so called targeted cancer therapy and are used for the treatment of different cancer types like non-small-lung-cancer (NSLC), head-and-neck-cancer, colon-rectal-cancer and pancreas-cancer [1,2,3,4]
In our cohort of patients treated with EGFR inhibiting monoclonal antibodies, miR-21 and miR-520e serum concentrations were negatively correlated with severity of skin rash (p-value 0.000582 and 1.53e-07 linear-trend-test) whereas for miR-31, a positive correlation was observed (p-value 9.01e-06 linear-trend-test)
This suggests that miR-21, miR-31 and miR-520e expression might be a treatment dependent marker for EGFRI induced skin rash
Summary
EGFR-InhibitorsEpidermal growth factor receptor inhibitors (EGFRI) belong to the so called targeted cancer therapy and are used for the treatment of different cancer types like non-small-lung-cancer (NSLC), head-and-neck-cancer (head-and-neck-ca), colon-rectal-cancer (colon-ca) and pancreas-cancer (pancreatic -ca) [1,2,3,4]. The highest evidence can be found for a preemptive treatment of EGFRI induced skin rash with oral tetracycline. For this treatment a double-blind placebo-controlled randomized trial and different randomized trials showed a significant reduction of the severity of skin toxicity in patients treated with tetracycline’s [14,15,16,17]. With a low evidence, due to a missing control cohort in the study, orally administrated isotretinoin and clindamycin could reduce grade 2–3 skin rash to grade 0–1 [19] With all these possible treatments of EGFRI induced skin rash, its treatment predictive value might get lost and new biomarkers will be needed
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