The tumor microenvironment is home to various types of cognate and non-cognate cell interactions.Here we comment on FENNEL a newly discovered form of intercellular communication, which is based on endoplasmic reticulum stress signaling.Through this mechanism transmitter cancer cells impart receiver Footstools cancer cells with resistance to secondary metabolic, pharmacologic and genotoxic stress, providing survival advantage.The implications of this finding are briefly discussed.