Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics
For patients with metastatic pancreatic cancer that are not eligible for surgery, signal-targeted therapies have so far failed to significantly improve survival. These therapeutic options have been tested in phase II/III clinical trials mostly in combination with the reference treatment gemcitabine....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-06-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/10/6/174 |
| _version_ | 1797765868775538688 |
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| author | Célia Cintas Thibaut Douché Nicole Therville Silvia Arcucci Fernanda Ramos-Delgado Céline Basset Benoît Thibault Julie Guillermet-Guibert |
| author_facet | Célia Cintas Thibaut Douché Nicole Therville Silvia Arcucci Fernanda Ramos-Delgado Céline Basset Benoît Thibault Julie Guillermet-Guibert |
| author_sort | Célia Cintas |
| collection | DOAJ |
| description | For patients with metastatic pancreatic cancer that are not eligible for surgery, signal-targeted therapies have so far failed to significantly improve survival. These therapeutic options have been tested in phase II/III clinical trials mostly in combination with the reference treatment gemcitabine. Innovative therapies aim to annihilate oncogenic dependency, or to normalize the tumoural stroma to allow immune cells to function and/or re-vascularisation to occur. Large scale transcriptomic and genomic analysis revealed that pancreatic cancers display great heterogeneity but failed to clearly delineate specific oncogene dependency, besides oncogenic Kras. Beyond these approaches, proteomics appears to be an appropriate approach to classify signal dependency and to identify specific alterations at the targetable level. However, due to difficulties in sampling, proteomic data for this pathology are scarce. In this review, we will discuss the current state of clinical trials for targeted therapies against pancreatic cancer. We will then highlight the most recent proteomic data for pancreatic tumours and their metastasis, which could help to identify major oncogenic signalling dependencies, as well as provide future leads to explain why pancreatic tumours are intrinsically resistant to signal-targeted therapies. We will finally discuss how studies on phosphatidylinositol-3-kinase (PI3K) signalling, as the paradigmatic pro-tumoural signal downstream of oncogenic Kras in pancreatic cancer, would benefit from exploratory proteomics to increase the efficiency of targeted therapies. |
| first_indexed | 2024-03-12T20:16:19Z |
| format | Article |
| id | doaj.art-2e46419e3ce244989e023c36c4d44550 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T20:16:19Z |
| publishDate | 2018-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2e46419e3ce244989e023c36c4d445502023-08-02T01:15:06ZengMDPI AGCancers2072-66942018-06-0110617410.3390/cancers10060174cancers10060174Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in ProteomicsCélia Cintas0Thibaut Douché1Nicole Therville2Silvia Arcucci3Fernanda Ramos-Delgado4Céline Basset5Benoît Thibault6Julie Guillermet-Guibert7INSERM U1037, CRCT, Université Paul Sabatier, 31037 Toulouse, FranceINSERM U1037, CRCT, Université Paul Sabatier, 31037 Toulouse, FranceINSERM U1037, CRCT, Université Paul Sabatier, 31037 Toulouse, FranceINSERM U1037, CRCT, Université Paul Sabatier, 31037 Toulouse, FranceINSERM U1037, CRCT, Université Paul Sabatier, 31037 Toulouse, FranceINSERM U1037, CRCT, Université Paul Sabatier, 31037 Toulouse, FranceINSERM U1037, CRCT, Université Paul Sabatier, 31037 Toulouse, FranceINSERM U1037, CRCT, Université Paul Sabatier, 31037 Toulouse, FranceFor patients with metastatic pancreatic cancer that are not eligible for surgery, signal-targeted therapies have so far failed to significantly improve survival. These therapeutic options have been tested in phase II/III clinical trials mostly in combination with the reference treatment gemcitabine. Innovative therapies aim to annihilate oncogenic dependency, or to normalize the tumoural stroma to allow immune cells to function and/or re-vascularisation to occur. Large scale transcriptomic and genomic analysis revealed that pancreatic cancers display great heterogeneity but failed to clearly delineate specific oncogene dependency, besides oncogenic Kras. Beyond these approaches, proteomics appears to be an appropriate approach to classify signal dependency and to identify specific alterations at the targetable level. However, due to difficulties in sampling, proteomic data for this pathology are scarce. In this review, we will discuss the current state of clinical trials for targeted therapies against pancreatic cancer. We will then highlight the most recent proteomic data for pancreatic tumours and their metastasis, which could help to identify major oncogenic signalling dependencies, as well as provide future leads to explain why pancreatic tumours are intrinsically resistant to signal-targeted therapies. We will finally discuss how studies on phosphatidylinositol-3-kinase (PI3K) signalling, as the paradigmatic pro-tumoural signal downstream of oncogenic Kras in pancreatic cancer, would benefit from exploratory proteomics to increase the efficiency of targeted therapies.http://www.mdpi.com/2072-6694/10/6/174pancreatic cancerproteomicsPI3K pathwayprecision medicinepredictor of therapeutic responseintegrated biologyproteo-genomics |
| spellingShingle | Célia Cintas Thibaut Douché Nicole Therville Silvia Arcucci Fernanda Ramos-Delgado Céline Basset Benoît Thibault Julie Guillermet-Guibert Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics Cancers pancreatic cancer proteomics PI3K pathway precision medicine predictor of therapeutic response integrated biology proteo-genomics |
| title | Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics |
| title_full | Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics |
| title_fullStr | Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics |
| title_full_unstemmed | Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics |
| title_short | Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics |
| title_sort | signal targeted therapies and resistance mechanisms in pancreatic cancer future developments reside in proteomics |
| topic | pancreatic cancer proteomics PI3K pathway precision medicine predictor of therapeutic response integrated biology proteo-genomics |
| url | http://www.mdpi.com/2072-6694/10/6/174 |
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