Melanoma and sex hormones: Pathogenesis, progressive disease and response to treatments.

Cutaneous melanoma represents the fifth tumor in terms of incidence in young adults, with a major involvement of males than females. Despite the significant changes in available effective treatments for cutaneous melanoma, there is still a proportion of patients that do not benefit long-term disease control with immune checkpoint inhibitors and/or BRAF/MEK inhibitors, and eventually develop progressive disease. In addition to the emerging biomarkers under investigation to understand resistance to treatments, recent studies resumed the role of sex hormones (estrogens, progesterone and androgens) in melanoma patients. In the last decades, the impact of sex hormones has been considered controversial in melanoma patients, but actual growing preclinical and clinical evidence underline the potential influence on melanoma cells' growth, tumor microenvironment, the immune system and consequently on the course of disease.This review will provide available insights on the role of sex hormones in melanoma pathogenesis, disease progression and response/resistance to systemic treatments. We will also offer an overview on the recent studies on the theme, describing the hormonal contribution to disease response and the interaction with targeted therapies and immune-checkpoint inhibitors in cutaneous melanoma patients, illustrating an insight into future research in this field.

Fatal Heart Failure Induced by Pazopanib in a Sarcoma Patient Previously Treated with Gemcitabine.

Gemcitabine is commonly used for various solid organ malignancies with rarely reported cardiac side effects such as cardiomyopathy. Pazopanib usually can cause arterial hypertension but cases of heart failure have recently been reported. We describe a case of fatal heart failure after treatment with gemcitabine and pazopanib in a 55-year-old female with sarcoma. Patient developed left ventricular dysfunction after gemcitabine treatment and acute heart failure after 22 days of pazopanib treatment which led to death. Physicians should be aware of the cardiotoxicity risk when managing the use of pazopanib especially in patients previously treated with other cardiotoxic drugs.