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.
| Original language | English |
|---|---|
| Pages (from-to) | 539-554 |
| Number of pages | 16 |
| Journal | Genes and Immunity |
| Volume | 20 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Sep 1 2019 |
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ASJC Scopus subject areas
- Immunology
- Genetics
- Genetics(clinical)
Cite this
Cell death pathologies : targeting death pathways and the immune system for cancer therapy. / Pentimalli, Francesca; Grelli, Sandro; Di Daniele, Nicola; Melino, Gerry; Amelio, Ivano.
In: Genes and Immunity, Vol. 20, No. 7, 01.09.2019, p. 539-554.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Cell death pathologies
T2 - targeting death pathways and the immune system for cancer therapy
AU - Pentimalli, Francesca
AU - Grelli, Sandro
AU - Di Daniele, Nicola
AU - Melino, Gerry
AU - Amelio, Ivano
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85058853093&partnerID=8YFLogxK
U2 - 10.1038/s41435-018-0052-x
DO - 10.1038/s41435-018-0052-x
M3 - Review article
C2 - 30563970
AN - SCOPUS:85058853093
VL - 20
SP - 539
EP - 554
JO - Genes and Immunity
JF - Genes and Immunity
SN - 1466-4879
IS - 7
ER -