Alterations in the TGF-β/BMP pathway due to loss-of-function mutations or deletions affecting SMAD4, FBXW7, ARID1A, or BMPR2 have previously been shown to correlate with decreased overall survival and to promote chemoresistance in multiple cancer types, such as CRC [11,13], ovarian cancer [79,80,81] and squamous cell carcinoma [82]. Here, SMAD4 is linked to cancer.