miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer

Abstract

One of the hallmarks of cancer is sustained angiogenesis. Favorable results have been reported in some breast cancer (BC) patients receiving antiangiogenic therapy with bevacizumab (Bev) in combination with chemotherapy, and further knowledge on how Bev can be optimally combined with conventional treatment to increase efficacy is strongly needed. In this randomized, neoadjuvant phase II clinical trial, 132 patients with HER2‐negative, nonmetastatic BC were treated with Bev in combination with sequential chemotherapy. Biopsies were sampled before treatment, after 12 weeks with anthracycline and after taxane therapy at week 25. MicroRNA (miRNA) expression profiling was performed on biopsies from each time point. Altogether, 241 biopsies were analyzed with the aim of identifying miRNA‐based biomarkers of response to therapy. Results from the miRNA analyses were reported for the ER‐positive cohort, which were previously demonstrated to benefit from antiangiogenic therapy in this study. For both treatment arms of this cohort, significantly different expression was observed for 217 miRNAs between objective responding and nonresponding patients before treatment initiation. These miRNAs have been linked to regulation of epithelial–mesenchymal transition, metastasis, and tumor growth, among other processes. Bev in combination with chemotherapy resulted in similar miRNA changes to chemotherapy alone. However, the deregulation of miRNA expression occurred earlier in the Bev arm. In both arms, tumor suppressor miRNAs were found upregulated after treatment, while oncogenic miRNAs were downregulated in the Bev arm. Patients responding to Bev showed a strong correlation between deregulated miRNAs and decreased proliferation score during the course of treatment, with downregulation of miR‐4465 as the strongest indicator of reduced proliferation. Integrative analyses at miRNA‐, gene‐, and protein expression further indicated a longitudinal decrease in proliferation. Altogether, the results indicate that proliferation might represent a predictive factor for increased Bev sensitivity, which may aid in the identification of patients who could potentially benefit from Bev.

Applying Serum Proteins and MicroRNA as Novel Biomarkers for Early-Stage Cervical Cancer Detection

“…Specifically, miRNA-200a, miRNA-25 and miRNA-486-5p demonstrated 1.38-fold, 1.45-fold and 1.93-fold elevated expression in cervical cancer patients in early stages (p < 0.001). We found that most of the miRNA showed less than 2-fold level of expression differences and we hypothesized that it was due to the early stage of cervical cancer, as several studies [25][26][27] found that the cancer development at early stage did not affect miRNA expression as much as that at late stage.…”

ctDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab

“…Particularly for cancers where new biopsies are difficult to obtain, the analysis of ctDNA can provide a tool for identifying treatment targets and monitoring treatment response, minimal residual disease and relapse. With the increasing numbers of clinical trials investigating the role of bevacizumab in cancer (ClinicalTrials.gov Identifiers NCT00790010, NCT03743428, NCT02884648, NCT03836066), commonly in combination with other drugs 29–33 , the discovery of an early biomarker for treatment response, using a method that allows repetitive, minimal invasive testing at low cost, would be of high value.…”

Non-coding RNAs as Putative Biomarkers of Cancer-Associated Cachexia

“…The initial studies, concerning the role of miRNAs in cancer occurrence, focused on patients-derived tumoral tissues and allowed the identification of specific signature able to stratify human cancers (Lu et al, 2005;Calin and Croce, 2006;Di Leva and Croce, 2013). In particular, miRNAs discriminate tumoral from non-tumoral tissues, or metastatic from non-metastatic tumors, or different histotypes of the same tumor type, or, in treated patients, responder from non-responder individuals Lindholm et al, 2019;Sokilde et al, 2019).…”