Malignant transformation can result in melanoma cells that resemble different stages of their embryonic development. Our gene expression analysis of human melanoma cell lines and patient tumors revealed that melanoma follows a two-dimensional differentiation trajectory that can be subclassified into four progressive subtypes. This differentiation model is associated with subtype-specific sensitivity to iron-dependent oxidative stress and cell death known as ferroptosis. Receptor tyrosine kinase-mediated resistance to mitogen-activated protein kinase targeted therapies and activation of the inflammatory signaling associated with immune therapy involves transitions along this differentiation trajectory, which lead to increased sensitivity to ferroptosis. Therefore, ferroptosis-inducing drugs present an orthogonal therapeutic approach to target the differentiation plasticity of melanoma cells to increase the efficacy of targeted and immune therapies.

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Objective To assess the prognostic significance of presentation serum albumin, clinical stage and CA125 levels in ovarian cancer. Design Retrospective analysis of data using a Cox proportional hazards model. Setting A district general hospital oncology unit. Subject One hundred and fourteen consecutive patients with epithelial ovarian cancer. Interventions Cytotoxic chemotherapy and surgery. Main outcome measure Survival. Results A linear increase in risk was observed with high log CA125 (P < 0.0001) and with low albumin (P < 0.0001). In late stage patients (III and IV) albumin is the best predictor of survival (P= 0.0006). The presence of ascites, blood transfusion, type of surgery or chemotherapy did not improve the predictive model. Conclusions CA125 and albumin can be used to identify prognostic subgroups independently of stage. Albumin alone can also be used as a predictor of survival. A simple classification of patients into three groups based on serum albumin of 41 g/l or more, 35 to 40 g/l and 34 g/l or less provides a clear separation of survival curves in the present group of patients.

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