The role of novel programmed cell death in head and neck squamous cell carcinoma: from mechanisms to potential therapies

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a common oral cancer with poor prognosis and for which no targeted therapeutic strategies are currently available. Accumulating evidence has demonstrated that programmed cell death (PCD) is essential in the development of HNSCC as a second messenger. PCD can be categorized into numerous different subroutines: in addition to the two well-known types of apoptosis and autophagy, novel forms of programmed cell death (e.g., necroptosis, pyroptosis, ferroptosis, and NETosis) also serve as key alternatives in tumorigenesis. Cancer cells are not able to avoid all types of cell death simultaneously, since different cell death subroutines follow different regulatory pathways. Herein, we summarize the roles of novel programmed cell death in tumorigenesis and present our interpretations of the molecular mechanisms with a view to the development of further potential therapies.

Exploring beyond Common Cell Death Pathways in Oral Cancer: A Systematic Review

“…While malignant cells develop strategies to escape or limit conventional cell death pathways, understanding of their ability to escape death by other mechanisms is much more limited [5]. Since 2018, the Nomenclature Committee on Cellular Death has classified PCD into 12 subtypes of death that differ in molecular mechanisms but may share small similarities in their morphological characteristics, ranging from a necrotic profile, that is, unprogrammed and with a disordered appearance, to an apoptotic profile with an organized profile [2,7]. However, an update proposed by Yan, Elbadawi and Efferth [3] divided cell deaths into three large groups based on activation of specific signaling pathways: (1) Non-programmed cell death (NPCD) or necrosis, (2) apoptotic programmed cell death (APCD) and (3) non-apoptotic programmed cell death (NAPCD), which differs from the apoptotic form because it does not maintain the integrity of the cell membrane and is independent of caspases.…”