Introduction

Many tumors overexpress TRF2 compared to healthy tissues, promoting carcinogenesis. In particular, breast cancer expresses high levels of TRF2 correlated with a worse prognosis. Triple negative breast cancer (TNBC) is a particularly aggressive tumor subtype, still lacking specific treatments. The present invention relates to microRNAs capable of inhibiting the expression of TRF2 in tumors.

 

Technical features

New anti-tumor drugs with molecular target against TRF2 over-expressing tumors, in those tumors in which TRF2 is more expressed than its expression in healthy tissue. It has been found that miR-182-3p, miR-519e-5p and miR-296-3p are efficient in modulating the expression of the TRF2 protein. Furthermore, miR-182-3p showed anti-proliferative properties in multiple triple negative breast cancer (TNBC) models, even in particularly resistant models. The miRNAs are encapsulated in lipid nanoparticles as a system that allows the molecules to be stabilized and conveyed in the bloodstream, preventing their degradation. The lipid nature also represents an advantage for the intracellular absorption process. The miRNAs can be used alone or in combination with each other. The types of tumor likely to be considered are: breast, cervical, colon, osteosarcoma, primary brain, metastatic brain. The present invention also relates to a possible combination of one or more of the miRNAs listed above with one or more anti-tumor drugs.

 

Possible Applications

• Diagnostic/therapeutic for tumors over-expressing the TRF2 protein;
• Obtain measurements of TRF2 expression in breast cancer samples in patients at risk of metastasis;
• Treat patients with breast cancer with adjuvant therapy even in the presence of favourable clinical-pathological characteristics.

Advantages

• Cancer treatment alternative to classical chemotherapy;
• Treatments based on miRNA activity in multiple preclinical models;
• Drugs which, for the first time, reduce the intratumoral expression of TRF2;
• Pharmaceutical composition of miRNA and pharmaceutically acceptable excipients/adjuvants.