TFAM and cancer: For example, mtDNA is decreased in gastric cancer, breast cancer, hepatocellular carcinoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma.9–13 By contrast, mtDNA copy number is increased in other types of cancer, including CRC.14–18 Recently, Guo et al. have reported that mtDNA depletion induced by mitochondrial transcription factor A (TFAM) mutation plays a promoting role in tumorigenesis and cisplatin resistance in MSI CRC.19 However, the effects of altering mtDNA copy number on the tumor progression of MSS CRC, the majority of CRC, are largely unknown.