Targeting the activated allosteric conformation of the endothelin receptor B in melanoma with an antibody-drug conjugate: mechanisms and therapeutic efficacy.

Background: Endothelin 1 receptors are one of the drivers of tumor progression in many cancers. Inhibition of their signaling pathways with antagonist drugs has been the subject of numerous clinical trials, but the results have not met expectations probably due to the high endothelin concentrations in the tumor microenvironment and their unusually high affinity for their receptors.

Methods: We previously reported the rendomab B49 antibody (RB49) exhibiting a preferential affinity for the activated conformation of human endothelin B receptor (ET), not displaced by high endothelin levels, and without any pharmacological properties that could inhibit the division of melanoma cells.

PROM2 overexpression induces metastatic potential through epithelial-to-mesenchymal transition and ferroptosis resistance in human cancers.

Introduction: Despite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin-2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio-target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma.

A Sub-Group of Kidney-Transplant Recipients with Highly Aggressive Squamous Cell Carcinoma Expressing Phosphorylated Serine392p53.

Cutaneous squamous cell carcinomas in kidney-transplant recipients are frequent, with an increasing incidence linked to long immunosuppression durations and exposure to ultraviolet radiation. p53 is at the cornerstone of ultraviolet-induced DNA damage, but the role of p53 post-translational modifications in this context is not yet deciphered. Here, we investigated the phosphorylation status of p53 at Serine 392 in 25 cutaneous squamous cell carcinomas in kidney-transplant recipients, compared with 22 non-transplanted patients.