By overcoming drug resistance (Ezrova et al., 2021) in patients with SMAD family member 4 gene (SMAD4)-deficient or Transforming Growth Factor-β (TGF-β) signaling-mediated pancreatic cancer, Mito-Tam contributes to the development of a rational predictive marker for mitochondrial-targeted therapy in pancreatic cancer patients with SMAD4 expression. Here, SMAD4 is linked to familial pancreatic carcinoma.