CONTEXT

The transmembrane receptor protein HER2 has a tyrosine kinase activity and is involved in the regulation of several genes linked to the transcription of cell cycle. HER2 is overexpressed in several types of cancer, as breast, ovary, colon, pancreas…

This protein is a well known target for anticancer treatments as Trastuzumab, a monoclonal antibody, HER2 bloking agent.

HER2 positive breast cancer show different responses to a trastuzumab treatment. In several cancer cases, Trastuzumab is not indicated to treat the tumor. Indeed, medical centers try to adapt the treatment according to preliminary pronostic on the response of each patient to a HER2 blocking agent treatment.

This prognostic can be done by the characterization of each patient tumoral genes expression profile, from 4 to 28 genes on tumor biopsy. This method is long, expensive and implies a biopsy.

TECHNICAL DESCRIPTION

The inventor has settled a novel methodology to predict each patient response to a HER2 blocking agent treatment. This methodology is based on a surprising discovery on connections between the negative response to Trastuzumab and the silent germinal polymorphism of a specific gene which down regulates the half-life of mRNA encoding several oncogenes, inflammatory factors and angiogenic factors.

Thisin vitro or ex vivo method comprises 2 steps :

=> The specific nucleotidic polymorphism detection on a biological sample
=> The determination of expression of genes of interest on a biological sample

BENEFITS

This method is related to prediction of treatment efficacy which is not currently available.

First of all it is very simple, fast, reliable, reproducible and relatively cheap compared to actual methods:
– No biopsy of the tumor is necessary (less risk related to this sampling). The analysis is based on a simple blood sample (5 to 10 mL) of the patient.
– Analysis involves simple and common molecular biology techniques.

INDUSTRIAL APPLICATIONS

The main application of this invention is the preliminary prognostic to the response of treatment of a cancer with an HER2 blocking agent. This methodology will help medical centres to adapt HER2 positive cancer treaments.

DEVELOPMENT STAGE

This methodology has been validated by inventors on a breast cancer patient cohort.