Treatment of HER2-dependent cancer

About 25% of primary human breast cancers are due to the deregulated expression of HER2 which is also found in many cancer types. HER2-targeted therapies have improved patients’ survival but both de novo and acquired resistance remain a challenge, as only 25% of the patients respond to the actual therapies. The team identified some miRNA including hsa miR-200b-3p and hsa-miR-429 from miR-200 family that are upregulated in HER2+ breast cancer cells and tumour samples. Their high level of expression is of bad prognosis for HER2+ breast cancer patients. Some of these miRNAs are also essential for HER2 expression and/or function. This allows to further stratify HER2+ breast cancer patients to offer a personalized treatment based on the modulation of miR-200b or miR-429. The team developed an optimized and vectorized anti-miRNA allowing specific inactivation of miR-429. Efficacy has been demonstrated in vitro in HER2+ cancer models of breast, gastric, ovarian and pancreatic origin as well as in a HER2+ breast cancer cell in ovo xenograft model.

Applications

• Diagnosis of HER2+ breast cancer based on miRNA expression level
• Evaluation of the prognosis of HER2+ breast cancer patients based on miRNA expression level
• Novel HER2-targeted therapy based on anti-miRNA delivery
• Treatment of HER2+ cancers

Competitive advantages

• Therapeutic efficacy on HER2 including forms resistant to the actual therapeutic arsenal
• MiRNAs level of expression can be assessed with non-invasive techniques
• Anti-miR-429 targets HER2 expression

Intellectual property

Treatment of HER2-dependent cancer using an agent that modulates the activity of a miRNA. Inventeurs: Faure C., Bourdoulous S., Domingot A. (WO/2019/081607)

Keywords

ERBB2 - HER2+ breast cancers - Targeted Therapies - MiRNA - Personalized medicine