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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-A02324-53 | Other Identifier | ANSM | |
| 2023-A00894-41 | Other Identifier | ANSM -étude ancillaire |
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| Name | Class |
|---|---|
| Institut National de la Santé Et de la Recherche Médicale, France | OTHER_GOV |
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Skin carcinomas are the most frequent cancers in the world, including basal cell carcinomas and cutaneous squamous cell carcinoma (cSCCs), with more than 60.000 new annual cases in France. Their incidence increases mainly due to ultraviolet (UV) exposure and population ageing. Then from 1994 to 2006, the incidence of cSCC has increased by 300%. CSCCs typically manifests as a spectrum from a precursor actinic keratosis (AK) - possible spontaneous regression at this stage- to in situ cSCC invasive cSCC and finally metastatic cSCC.
Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation and how it influences further the bioenergetic behavior of tumors.
By applying a quantitative proteomic approach, the consortium has recently found that specific metabolic modifications precede cSCC.
This study will investigate the role of energy metabolism in malignant transformation of premalignant skin lesions into cSCC, and in cSCC progression, with correlation with clinical characteristics and metastatic outcomes. Using several cutting-edge technologies in human samples, the team will evaluate whether targeting energy metabolism has the potential to be used as curative treatments for cSCC and whether pre-determined metabolic alterations could be exploited as new preventive strategies. These modifications in energy metabolism could be used as prognostic and diagnostic biomarkers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with actinic keratoses | Experimental |
| |
| patients with squamous cell carcinoma in situ | Experimental |
| |
| patients with squamous cell carcinomas | Experimental |
| |
| patient with invasive metastates | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| biopsy | Other | Skin biopsies will be performed according to standard practices in the usual aseptic conditions, the operator wearing sterile gloves. A circular knife 3 mm will be used. Procedure interventions do not involve a drug or a device. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients who have a glycolysis profile (proteomic analysis liquid chromatography-mass spectrometry (LC-MS/MS)) | Metabolic profiling of different stages of carcinogenesis: glycolysis, oxidative phosphorylation | Day 1 |
| Proportion of patients who have an oxidative profile (proteomic analysis liquid chromatography-mass spectrometry (LC-MS/MS)) | Metabolic profiling of different stages of carcinogenesis: glycolysis, oxidative phosphorylation | Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of skin differentiation markers | % of samples in each category (AK, in situ, ...) that present differentiation features are assessed by immunostaining of loricrin, filaggrin, K10 | Day 1 |
| Evaluation of cSCC aggressiveness markers |
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Inclusion Criteria:
Every patient with suspected lesion :
Patients 18 years of age or older,
Patients with suspected AK or BCC lesions (in situ, infiltrating or metastatic),
Patient able to sign a consent form,
Patient affiliated with a Social Security system.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marie BEYLOT-BARRY, MD, PhD | University Hospital, Bordeaux | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Saint-André - CHU de Bordeaux | Bordeaux | 33000 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25542180 | Background | Obre E, Rossignol R. Emerging concepts in bioenergetics and cancer research: metabolic flexibility, coupling, symbiosis, switch, oxidative tumors, metabolic remodeling, signaling and bioenergetic therapy. Int J Biochem Cell Biol. 2015 Feb;59:167-81. doi: 10.1016/j.biocel.2014.12.008. Epub 2014 Dec 24. | |
| 29925003 | Background |
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| ID | Term |
|---|---|
| D002280 | Carcinoma, Basal Cell |
| D055623 | Keratosis, Actinic |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D001706 | Biopsy |
| ID | Term |
|---|---|
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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% of samples expressing aggressive markers will be assessed by evaluating the proliferation index, degree of differentiation, invasion beyond subcutaneous fat, perineural invasion, vascular invasion level of infiltration following immunohistochemistry analyses on formalin-fixed paraffin-embedded tissue sections.
| Day 1 |
| Evaluation of skin apoptotic markers | % of samples with high apoptotic cell death level will be assessed by immunostaining using antibody against cleaved caspase-3. | Day 1 |
| Evaluation of mitochondrial metabolism on skin biopsies | % of samples with high mitochondrial activity will be evaluated by comparing oxygen consumption rate by different fresh samples. | Day 1 |
| Evaluation of cancer proliferative features on skin biopsies | % of samples that are highly proliferative will be calculated by measuring the ability of colony formation (SRB Test) and cell cycle progression (flow cytometer, western). | Day 1 |
| Hosseini M, Dousset L, Mahfouf W, Serrano-Sanchez M, Redonnet-Vernhet I, Mesli S, Kasraian Z, Obre E, Bonneu M, Claverol S, Vlaski M, Ivanovic Z, Rachidi W, Douki T, Taieb A, Bouzier-Sore AK, Rossignol R, Rezvani HR. Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation. Cell Rep. 2018 Jun 19;23(12):3621-3634. doi: 10.1016/j.celrep.2018.05.060. |
| 31551419 | Background | Hosseini M, Dousset L, Michon P, Mahfouf W, Muzotte E, Bergeron V, Bortolotto D, Rossignol R, Moisan F, Taieb A, Bouzier-Sore AK, Rezvani HR. UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis. Oncogenesis. 2019 Sep 24;8(10):52. doi: 10.1038/s41389-019-0161-z. |
| 30878676 | Background | Mahfouf W, Hosseini M, Muzotte E, Serrano-Sanchez M, Dousset L, Moisan F, Rachidi W, Taieb A, Rudolf J, Rezvani HR. Loss of Epidermal HIF-1alpha Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress. J Invest Dermatol. 2019 Sep;139(9):2016-2028.e7. doi: 10.1016/j.jid.2019.01.035. Epub 2019 Mar 13. |
| 40577595 | Result | Dousset L, Khalife F, Chalopin-Fillot D, Dartigues B, Naji F, Mahfouf W, Muzotte E, Rousseau B, Amoedo N, Claverol S, Bondaz M, Beltzung F, Jullie ML, Vergier B, Taieb A, Favot-Laforge L, Rossignol R, Beylot-Barry M, Nikolski M, Rezvani HR. Metabolism-based scoring of cutaneous squamous cell carcinoma to predict tumour features and responses to treatment with dihydroorotate dehydrogenase inhibitors. Br J Dermatol. 2025 Oct 17;193(5):936-947. doi: 10.1093/bjd/ljaf253. |
| D018295 |
| Neoplasms, Basal Cell |
| D011230 | Precancerous Conditions |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |