Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities

Multiple myeloma is a plasma cell skeletal malignancy. While therapeutic agents such as bortezomib and lenalidomide have significantly improved overall survival, the disease is currently incurable with the emergence of drug resistance limiting the efficacy of chemotherapeutic strategies. Failure to cure the disease is in part due to the underlying genetic heterogeneity of the cancer. Myeloma progression is critically dependent on the surrounding microenvironment. Defining the interactions between myeloma cells and the more genetically stable hematopoietic and mesenchymal components of the bone microenvironment is critical for the development of new therapeutic targets. In this review, we discuss recent advances in our understanding of how microenvironmental elements contribute to myeloma progression and therapeutically, how those elements can or are currently being targeted in a bid to eradicate the disease

Cardiovascular and Central Nervous System Toxicity by Anticancer Drugs in Breast Cancer Patients

Breast cancer is one of the most malignant diseases, associated with high rate mortality. In this chapter a particular attention is paid on cardiovascular and central nervous system toxicity induced by chemotherapeutic agents used for both primary and metastatic treatment of this life-threatening pathology. With respect to traditional drugs, including anthracyclines, taxanes, and fluoropyrimidines, the more recent targeted therapies, such as human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF), aimed to ameliorate anticancer activity and to reduce toxic effects by affecting more specific molecular sites. However, despite the improvement in breast cancer treatment, these novel drugs were also found to be associated, even if at a lesser extent, with important side effects, such as cardiotoxicity, with consequent heart failure. For this reason, the cardiovascular and brain safety profile of all anticancer drugs and protocols remains important items to be carefully evaluated in breast cancer patients