Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer that is strongly associated with poor prognosis and short median survival times. In stark contrast to the progress seen in other cancer types in recent decades, discoveries of new treatments in PDAC have been few and far between and there h...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/19/4834 |
| _version_ | 1797516744182464512 |
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| author | Hannah Pook Siim Pauklin |
| author_facet | Hannah Pook Siim Pauklin |
| author_sort | Hannah Pook |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer that is strongly associated with poor prognosis and short median survival times. In stark contrast to the progress seen in other cancer types in recent decades, discoveries of new treatments in PDAC have been few and far between and there has been little improvement in overall survival (OS). The difficulty in treating this disease is multifactorial, contributed to by late presentation, difficult access to primary tumour sites, an ‘immunologically cold’ phenotype, and a strong tendency of recurrence likely driven by cancer stem cell (CSC) populations. Furthermore, apparently contrasting roles of tumour components (such as fibrotic stroma) and intracellular pathways (such as autophagy and TGFβ) have made it difficult to distinguish beneficial from detrimental drug targets. Despite this, progress has been made in the field, including the determination of mFOLFIRINOX as the standard-of-care adjuvant therapy and the discovery of KRAS<sup>G12C</sup> mutant inhibitors. Moreover, new research, as outlined in this review, has highlighted promising new approaches including the targeting of the tumour microenvironment, enhancement of immunotherapies, epigenetic modulation, and destruction of CSCs. |
| first_indexed | 2024-03-10T07:05:08Z |
| format | Article |
| id | doaj.art-beea336eedb14679b01a9cb2f090a96a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:05:08Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-beea336eedb14679b01a9cb2f090a96a2023-11-22T15:53:03ZengMDPI AGCancers2072-66942021-09-011319483410.3390/cancers13194834Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal AdenocarcinomaHannah Pook0Siim Pauklin1Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Old Road, University of Oxford, Oxford OX3 7LD, UKBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Old Road, University of Oxford, Oxford OX3 7LD, UKPancreatic ductal adenocarcinoma (PDAC) is a type of cancer that is strongly associated with poor prognosis and short median survival times. In stark contrast to the progress seen in other cancer types in recent decades, discoveries of new treatments in PDAC have been few and far between and there has been little improvement in overall survival (OS). The difficulty in treating this disease is multifactorial, contributed to by late presentation, difficult access to primary tumour sites, an ‘immunologically cold’ phenotype, and a strong tendency of recurrence likely driven by cancer stem cell (CSC) populations. Furthermore, apparently contrasting roles of tumour components (such as fibrotic stroma) and intracellular pathways (such as autophagy and TGFβ) have made it difficult to distinguish beneficial from detrimental drug targets. Despite this, progress has been made in the field, including the determination of mFOLFIRINOX as the standard-of-care adjuvant therapy and the discovery of KRAS<sup>G12C</sup> mutant inhibitors. Moreover, new research, as outlined in this review, has highlighted promising new approaches including the targeting of the tumour microenvironment, enhancement of immunotherapies, epigenetic modulation, and destruction of CSCs.https://www.mdpi.com/2072-6694/13/19/4834pancreatic cancerPDACepigeneticsmetabolismcancer stem cellscancer therapy |
| spellingShingle | Hannah Pook Siim Pauklin Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma Cancers pancreatic cancer PDAC epigenetics metabolism cancer stem cells cancer therapy |
| title | Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma |
| title_full | Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma |
| title_fullStr | Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma |
| title_short | Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma |
| title_sort | mechanisms of cancer cell death therapeutic implications for pancreatic ductal adenocarcinoma |
| topic | pancreatic cancer PDAC epigenetics metabolism cancer stem cells cancer therapy |
| url | https://www.mdpi.com/2072-6694/13/19/4834 |
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