SMAD4 and ovarian carcinoma: We present evidence demonstrating that exosomes derived from platinum-resistant EOC cells can transfer a portion of their chemo-resistant phenotype to platinum-sensitive cells and this increase in resistance corresponds with increased EMT and mutations in SMAD4. SMAD4 has been shown to be necessary for the transcription of EMT related genes through SMAD4/SMAD3 signaling [81] and EMT has been well established as a mediator of drug resistance in ovarian cancer [15, 99–101].