Caspase-Independent Pathways of Programmed Cell Death: The Unraveling of New Targets of Cancer Therapy?

Programmed Cell Death (PCD) is considered to be a pathological form of cell death when mediated by an intracellular program and it balances cell death with survival of normal cells. Pyroptosis, a type of PCD, is induced by the inflammatory caspase cleavage of gasdermin D (GSDMD) and apoptotic caspase cleavage of gasdermin E (GSDME). This review aims to summarize the latest molecular mechanisms about pyroptosis mediated by pore-forming GSDMD and GSDME proteins that permeabilize plasma and mitochondrial membrane activating pyroptosis and apoptosis. We also discuss the potentiality of pyroptosis as a therapeutic target in human diseases. Blockade of pyroptosis by compounds can treat inflammatory disease and pyroptosis activation contributes to cancer therapy.

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Gastrointestinal disorders as immune-related adverse events

Exploration of Targeted Anti-tumor Therapy ◽

10.37349/etat.2021.00039 ◽

2021 ◽

Author(s):

Daniele Balducci ◽

Claudia Quatraccioni ◽

Antonio Benedetti ◽

Marco Marzioni ◽

Luca Maroni

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Programmed Cell Death ◽

Adverse Events ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Survival Rates ◽

Programmed Cell Death 1 ◽

Anti Cancer ◽

Life Threatening

Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care. IrAEs may affect all the organs, but they are most commonly seen in skin, lungs, endocrine glands and in the gastrointestinal tract where small bowel, colon, the liver and/or the pancreas can be involved. Despite being usually mild and self-resolving, irAEs may present in severe and life-threatening forms, causing the withdrawal of anti-cancer therapy. IrAEs, therefore, represent a challenging condition to manage that often requires the cooperation between the oncologists and the gastroenterologists in order to identify and treat them adequately.

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Targeting BCL-2 regulated apoptosis in cancer

Open Biology ◽

10.1098/rsob.180002 ◽

2018 ◽

Vol 8 (5) ◽

pp. 180002 ◽

Cited By ~ 114

Author(s):

Kirsteen J. Campbell ◽

Stephen W. G. Tait

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Programmed Cell Death ◽

Protein Family ◽

Mitochondrial Apoptosis ◽

Tumour Development ◽

A Cell

The ability of a cell to undergo mitochondrial apoptosis is governed by pro- and anti-apoptotic members of the BCL-2 protein family. The equilibrium of pro- versus anti-apoptotic BCL-2 proteins ensures appropriate regulation of programmed cell death during development and maintains organismal health. When unbalanced, the BCL-2 family can act as a barrier to apoptosis and facilitate tumour development and resistance to cancer therapy. Here we discuss the BCL-2 family, their deregulation in cancer and recent pharmaceutical developments to target specific members of this family as cancer therapy.

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