Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.
Role of the nucleus and mitochondria in the origin of tumors. Summary of a role of the mitochondria in the origin of tumorigenesis, as we previously described (Seyfried, 2012d; Seyfried et al., 2014). Normal cells are shown in green with nuclear and mitochondrial morphology indicative of normal gene expression and respiration, respectively. Tumor cells are shown in red with abnormal nuclear and mitochondrial morphology indicative of genomic instability and abnormal respiration, respectively. “(1) Normal cells beget normal cells. (2) Tumor cells beget tumor cells. (3) Transfer of a tumor cell nucleus into a normal cytoplasm begets normal cells, despite the presence of the tumor-associated genomic abnormalities. (4) Transfer of a normal cell nucleus into a tumor cell cytoplasm begets dead cells or tumor cells, but not normal cells. The results suggest that nuclear genomic defects alone cannot account for the origin of tumors, and that normal mitochondria can suppress tumorigenesis” (Seyfried, 2012d). Original diagram from Jeffrey Ling and Thomas N. Seyfried, with permission.