Integration of EMT and cellular survival instincts in reprogramming of programmed cell death to anastasis

Apoptosis is a tightly controlled, coordinated cellular event responsible for inducing programmed cell death to rid the body of defective or unfit cells. Inhibition of apoptosis is, therefore, an essential process for cancer cells to harness. Genomic variants in apoptotic-controlling genes are highly prevalent in cancer and have been identified to induce pro-proliferation and pro-survival pathways, rendering cancer cells resistant to apoptosis. Traditional understanding of apoptosis defines it as an irreversible process; however, growing evidence suggests that apoptosis is a reversible process from which cells can escape, even after the activation of its most committed stages. The mechanism invoked to reverse apoptosis has been termed anastasis and poses challenges for the development and utilization of chemotherapeutic agents. Anastasis has also been identified as a mechanism by which cells can recover from apoptotic lesions and revert back to its previous functioning state. In this review, we intend to focus the attention of the reader on the comprehensive role of survival, metastasis, and epithelial mesenchymal transition (EMT), as well as DNA damage repair mechanisms in promoting anastasis. Additionally, we will emphasize the mechanistic consequences of anastasis on drug resistance and recent rational therapeutic approaches designed to combat this resistance.