Non-Apoptotic Cell Death Mechanisms and their Therapeutic Significance

When the homeostatic equilibrium between cell proliferation and cell death breaks down and cells begin to proliferate uncontrollably, a cancer is formed. The cancer cells eventually acquire resistance against inherently executable apoptosis and against classical apoptosis-inducing drugs. The cells acquire apoptosis resistance through multiple mechanisms. For example, by downregulating proapoptotic proteins or upregulating antiapoptotic proteins, they shield themselves from both internal and external cues of the programmed cell death. Refusal of cells to undergo apoptosis poses a major challenge in targeted chemotherapies. Therefore, alternative strategies are being explored to effect cell death in apoptosis-resistant tumors.

There are several cell death mechanisms that operate with partial or no dependence on the components of apoptosis. These mechanisms include; methuosis, necroptosis, NETosis, pyronecrosis, pyroptosis, entosis, ferroptosis, lysosome-dependent cell death, and parthanatos. Preliminary investigations suggest that these pathways hold immense clinical potential. For example, methuosis ¬¬– a cell death characterized by vacuolization of macropinosomes and endosomes – can be induced in many cancer cells that are resistant to apoptosis. Similarly, ferroptosis eliminates many types of apoptosis-resistant cancer cells. Exploration of non-apoptotic cell death mechanisms offers a repertoire of options for the therapeutic intervention of apoptosis-resistant cancers. The goal of this research topic is to provide an overview of current knowledge and latest discoveries in the area of non-apoptotic cell death mechanisms and their therapeutic significance.

Cancer therapeutic research is an ever-evolving battlefield where the human intelligence is poised against the drug-evasion strategies of cancer cells. The aim of this Research Topic is to bring together cutting-edge research and comprehensive review articles from the field of non-apoptotic cell death mechanisms and their therapeutic potential. Contributions from investigators working in this area are invited. Studies involving intrinsic or chemical-induced induction of non-apoptotic cell death, mechanisms of apoptosis resistance, and co-induction of multiple cell death mechanisms in heterogenous tumors, are especially welcome. Review articles should have detailed and lucid illustrations and verifiable citations of original, relevant, and preferably, recent scientific articles.