Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy?
Resistance to EGFR-targeted therapy is a major obstacle on the road to effective treatment options for head and neck cancers. During the search for underlying mechanisms and regulators of this resistance, there were several indications that EGFR-targeted therapy resistance is (partially) mediated by...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/24/6128 |
| _version_ | 1797461054727389184 |
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| author | Hannah Zaryouh Jinthe Van Loenhout Marc Peeters Jan Baptist Vermorken Filip Lardon An Wouters |
| author_facet | Hannah Zaryouh Jinthe Van Loenhout Marc Peeters Jan Baptist Vermorken Filip Lardon An Wouters |
| author_sort | Hannah Zaryouh |
| collection | DOAJ |
| description | Resistance to EGFR-targeted therapy is a major obstacle on the road to effective treatment options for head and neck cancers. During the search for underlying mechanisms and regulators of this resistance, there were several indications that EGFR-targeted therapy resistance is (partially) mediated by aberrant signaling of the PI3K/Akt pathway. Genomic alterations in and/or overexpression of major components of the PI3K/Akt pathway are common in HNSCC tumors. Therefore, downstream effectors of the PI3K/Akt pathway serve as promising targets in the search for novel therapeutic strategies overcoming resistance to EGFR inhibitors. As both the EGFR/Ras/Raf/MAPK and the PI3K/Akt pathway are involved in autophagy, combinations of EGFR and PI3K/Akt pathway inhibitors can induce an autophagic response in tumor cells. This activation of autophagy can be seen as a “double-edge sword”, depending on the cellular context. Autophagy is largely known as a cytoprotective mechanism, but it can also be a mechanism of programmed (autophagic) cell death. The activation of autophagy during anti-cancer treatment is, therefore, not necessarily a bad sign. However, in HNSCC, the role of therapy-induced autophagy as an anti-tumor mechanism is still largely unclear. Further research is warranted to understand the potential of combination treatments targeting both the EGFR and PI3K/Akt pathway. |
| first_indexed | 2024-03-09T17:13:57Z |
| format | Article |
| id | doaj.art-03c98c50f9bc4ce5831bb20c551e7cb0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:13:57Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-03c98c50f9bc4ce5831bb20c551e7cb02023-11-24T13:46:38ZengMDPI AGCancers2072-66942022-12-011424612810.3390/cancers14246128Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy?Hannah Zaryouh0Jinthe Van Loenhout1Marc Peeters2Jan Baptist Vermorken3Filip Lardon4An Wouters5Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, 2610 Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, 2610 Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, 2610 Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, 2610 Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, 2610 Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, 2610 Antwerp, BelgiumResistance to EGFR-targeted therapy is a major obstacle on the road to effective treatment options for head and neck cancers. During the search for underlying mechanisms and regulators of this resistance, there were several indications that EGFR-targeted therapy resistance is (partially) mediated by aberrant signaling of the PI3K/Akt pathway. Genomic alterations in and/or overexpression of major components of the PI3K/Akt pathway are common in HNSCC tumors. Therefore, downstream effectors of the PI3K/Akt pathway serve as promising targets in the search for novel therapeutic strategies overcoming resistance to EGFR inhibitors. As both the EGFR/Ras/Raf/MAPK and the PI3K/Akt pathway are involved in autophagy, combinations of EGFR and PI3K/Akt pathway inhibitors can induce an autophagic response in tumor cells. This activation of autophagy can be seen as a “double-edge sword”, depending on the cellular context. Autophagy is largely known as a cytoprotective mechanism, but it can also be a mechanism of programmed (autophagic) cell death. The activation of autophagy during anti-cancer treatment is, therefore, not necessarily a bad sign. However, in HNSCC, the role of therapy-induced autophagy as an anti-tumor mechanism is still largely unclear. Further research is warranted to understand the potential of combination treatments targeting both the EGFR and PI3K/Akt pathway.https://www.mdpi.com/2072-6694/14/24/6128HNSCCEGFRPI3K/Aktcetuximabresistanceautophagy |
| spellingShingle | Hannah Zaryouh Jinthe Van Loenhout Marc Peeters Jan Baptist Vermorken Filip Lardon An Wouters Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy? Cancers HNSCC EGFR PI3K/Akt cetuximab resistance autophagy |
| title | Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy? |
| title_full | Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy? |
| title_fullStr | Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy? |
| title_full_unstemmed | Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy? |
| title_short | Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy? |
| title_sort | co targeting the egfr and pi3k akt pathway to overcome therapeutic resistance in head and neck squamous cell carcinoma what about autophagy |
| topic | HNSCC EGFR PI3K/Akt cetuximab resistance autophagy |
| url | https://www.mdpi.com/2072-6694/14/24/6128 |
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