Alterations in the molecular mechanisms of cell death are a common feature of cancer. These alterations enable malignant cells to survive intrinsic death signalling leading to accumulation of genetic aberrations and helping them to cope with adverse conditions. Regulated cell death has historically been exclusively associated with classical apoptosis; however, increasing evidence indicates that several alternative mechanisms orchestrate multiple death pathways, such as ferroptosis, entosis, necroptosis and immunogenic cell death, each with distinct underlying molecular mechanisms. Although pharmacological targeting of cell death pathways has been the subject of intensive efforts in recent decades with a dominant focus on targeting apoptosis, the identification of these novel death pathways has opened additional venues for intervention in cancer cells and the immune system. In this mini-review, we cover some recent progress on major recently emerged cell death modalities, emphasizing their potential clinical and therapeutic implications. We also discuss the interplay between cell death and immune response, highlighting the potential of the combination of traditional anticancer therapy and immunocheckpoint blockade. While attempting to stimulate discussion and draw attention to the possible clinical impact of these more recently emerged cell death modalities, we also cover the major progress achieved in translating strategies for manipulation of apoptotic pathways into the clinic, focusing on the attempts to target the anti-apoptotic protein BCL2 and the tumour suppressor p53.

Pentimalli, F., Grelli, S., Di Daniele, N., Melino, G., Amelio, I. (2019). Cell death pathologies: targeting death pathways and the immune system for cancer therapy. GENES AND IMMUNITY, 20(7) [10.1038/s41435-018-0052-x].

Cell death pathologies: targeting death pathways and the immune system for cancer therapy

Grelli S.;Di Daniele N.;Melino G.;Amelio I.
2019

Abstract

Alterations in the molecular mechanisms of cell death are a common feature of cancer. These alterations enable malignant cells to survive intrinsic death signalling leading to accumulation of genetic aberrations and helping them to cope with adverse conditions. Regulated cell death has historically been exclusively associated with classical apoptosis; however, increasing evidence indicates that several alternative mechanisms orchestrate multiple death pathways, such as ferroptosis, entosis, necroptosis and immunogenic cell death, each with distinct underlying molecular mechanisms. Although pharmacological targeting of cell death pathways has been the subject of intensive efforts in recent decades with a dominant focus on targeting apoptosis, the identification of these novel death pathways has opened additional venues for intervention in cancer cells and the immune system. In this mini-review, we cover some recent progress on major recently emerged cell death modalities, emphasizing their potential clinical and therapeutic implications. We also discuss the interplay between cell death and immune response, highlighting the potential of the combination of traditional anticancer therapy and immunocheckpoint blockade. While attempting to stimulate discussion and draw attention to the possible clinical impact of these more recently emerged cell death modalities, we also cover the major progress achieved in translating strategies for manipulation of apoptotic pathways into the clinic, focusing on the attempts to target the anti-apoptotic protein BCL2 and the tumour suppressor p53.
Pubblicato
Rilevanza internazionale
Recensione
Esperti anonimi
Settore MED/07 - Microbiologia e Microbiologia Clinica
English
Pentimalli, F., Grelli, S., Di Daniele, N., Melino, G., Amelio, I. (2019). Cell death pathologies: targeting death pathways and the immune system for cancer therapy. GENES AND IMMUNITY, 20(7) [10.1038/s41435-018-0052-x].
Pentimalli, F; Grelli, S; Di Daniele, N; Melino, G; Amelio, I
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/211483
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