PMAIP1 and cancer: Both MTHFD2 (a member of the mitochondrial glycine biosynthetic pathway) and PMAIP1 (known to mediate p53-dependent apoptosis via mitochondrial dysfunction) highlight the significance of the mitochondria to pemetrexed response and are consistent with recent studies that aim to therapeutically target the mitochondria in order to increase sensitivity of cancer cells to apoptosis34.