Estrogen-related receptor alpha agonists for the treatment of bone metastases

Bone is the most common metastatic site for breast cancer. The estrogen-related receptor alpha (ERRa) has been implicated in breast cancer cell dissemination to the bone from the primary tumor. However, its role after tumor cell anchorage in the bone microenvironment remains elusive. Here, the inventors reveal that ERRa inhibits the progression of bone metastases of breast cancer cells by increasing the immune activity of the bone microenvironment. Over-expressing ERRa in breast cancer bone metastases induced the expression of the chemokines CCL17 and CCL20 and repressed the production of transforming growth factor beta 3 (TGF-B3). Subsequently, CD8+ T lymphocytes recruited to the bone metastases escaped TGF-a signaling control were endowed with exacerbated cytotoxic features and metastases were strongly decreased. The clinical relevance of the findings in mice was confirmed in over 248 breast cancer patients. Thus, the inventors propose to consider ERRa expression, as a biomarker predictive of BM response to immunotherapies and /or as a good prognosis marker in BM progression once established, opening the path towards to the clinical use of ERRa agonist to relieve patients with ERRa positive BM after primary tumor resection.

Keywords: Metastases, PD1/PDL1 resistance, Immuno-Oncology
Patent Application number: EP20 305 290.7 on 19/03/20 - PCT/EP2021/056931 on 18/03/2021

Reference:

BIO20025-D1

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Pierre MAZOT
Pierre MAZOT
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Patent filling date: 2020-03-19

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