The prevailing mechanism of action of chemotherapeutic drugs has been challenged 
by the role of ceramide, a second messenger, shown to induce apoptosis, 
differentiation, growth arrest, senescence, and autophagy in different cells 
(Chabner BA, Roberts TG Jr, Nat Rev Cancer 5:65-72, 2005; Jacobi J et al, Cell 
Signal 29:52-61, 2017; Rotolo J et al, J Clin Invest 122:1786-1790, 2012; Truman 
JP et al, PLoS One 5:e12310, 2010). Certain chemotherapeutic drugs activate the 
acid sphingomyelinase (ASMase)/ceramide pathway, generating ceramide in the 
tumor endothelium and this microvascular dysfunction is crucial for the tumor 
response. Ceramide has fusigenic properties and as such, when generated within 
the plasma membrane, initiates the oligomerization of ceramide-and 
cholesterol-rich domains in the outer leaflet of the plasma membrane, leading to 
the formation of ceramide-rich microdomains/platforms (CRP) (Jacobi J et al, 
Cell Signal 29:52-61, 2017; Truman JP et al, PLoS One 5:e12310, 2010; van Hell 
AJ et al, Cell Signal 34:86-91, 2017; Hajj C, Haimovitz-Friedman A, Handb Exp 
Pharmacol 216:115-130, 2013) known as "signaling platform." This chapter will 
discuss the generation, detection, and quantitation of CRP and their possible 
modulation in endothelial cells, in vitro and in vivo in response to certain 
chemotherapeutic drugs.