4. Conclusion:
We report herein that 5,6-ECs are at the center of a newly discovered
metabolic branch that controls carcinogenesis (Fig 4). The
identification of oncosterone, its biosynthetic pathway and its
effectors, highlights the existence of interesting targets for the
development of anticancer drugs applicable for TNBC treatment (Fig 5).
This is reminiscent of the development of targeted therapeutic
strategies against the tumour promoter 17β-oestradiol for ER(+)-BC
treatment (Simpson & Santen, 2015). On the other hand, studies of the
5,6α-EC metabolism in normal tissues led to the identification of DDA.
Surprisingly DDA was found to display tumour suppressor properties on BC
through the activation of cell differentiation and death programs, and
the inhibition of oncosterone biosynthesis, highlighting the existence
of a metabolic balance between the tumour promoteur oncosterone and the
tumour suppressor DDA. This opens up new options for the development of
new anticancer agents targeting the oncosterone pathway in BC and new
strategies for the chemoprevention of BC. This also provides a new
rational at the molecular level to study potential relationships that
may exist between cholesterol, diet and BC oncogenesis programs
(Silvente-Poirot, Dalenc & Poirot, 2018).