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From the Characterization of the Cholesterol-epoxide Pathway Deregulation to New Therapeutic Perspectives in Breast Cancers

NCT02863900 · Status: UNKNOWN · Phase: NA · Type: INTERVENTIONAL · Enrollment: 350

Last updated 2016-08-11

No results posted yet for this study

Summary

The main objective of our project is to further characterize the deregulation of CE (Cholesterol Epoxides) metabolism in different moleculars subtypes of BC (BC=Breast Cancer) (luminal A and B, HER2+ and triple negative). We will study not only the level of expression of the enzymes involved in this pathway by immuno-histochemistry, all the enzymes involved were identified in our preclinical work (GSTA1 (Glutathione S-Transferase A1 ), DHCR7, D8D7I, 11βHSD2 (11β-hydroxysteroid dehydrogenase of type 2 )), but also the metabolite rates of CE (hydrolyses cholesterols-5,6-epoxide ), CT (into cholestane-3β, 5α, 6β triol ), DDA (Dendrogenin A)and OCDO (6-oxo-cholestan-3β, 5α-diol ). Our preliminary results demonstrate the feasibility of these dosages. We will also establish whether these deregulations are i) correlated with different histo-prognostic parameters (pN (N= Node), pT (T= Tumor) , EV, TIL…) but also clinical ii) an independent prognostic parameter of BC in terms of disease-free survival, metastasis-free survival and overall survival. The cohort consists of 350 cases of BC, treated between 2009 and 2011 as well as all relevant clinical informations. In parallel, we will continue our preclinical work by characterizing the targets and mechanisms of action of OCDO. Our preliminary results indicate that OCDO is a modulator of the glucocorticoid receptor (GR), which could be target to inhibit this pathway. On the other hand, we will characterize in the same manner as in human tumors, the deregulations of the CE metabolism in vitro and in vivo (including xenografts in mice of human tumors, in collaboration with Roman-Roman S) on a representative panel of BC molecular subtypes, sensitive or not usually administered in clinical treatment and study the anti-tumor effect of various "anti-OCDO" therapies (therapies preventing its production such as Tam (tamoxifen) or DDA, inhibitor of the enzyme producing OCDO, or an inhibitor of the GR (glucocorticoid receptor )), alone or in combination with conventional therapies

Conditions

Interventions

OTHER

cohort of BC of each subtypes

Sponsors & Collaborators

  • Institut Claudius Regaud

    lead OTHER

Principal Investigators

  • Florence DALENC, MD · Institut Claudius Regaud

Study Design

Allocation
NA
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2016-12-31
Primary Completion
2019-12-31
Completion
2019-12-31

Countries

  • France

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02863900 on ClinicalTrials.gov