Faculty of Medicine
Library of the School of Health Sciences

2020-02-28

2019

Koustas Evangelos

Παπαβασιλείου Αθανάσιος, Καθηγητής, Ιατρικής Σχολής, ΕΚΠΑ
Θεοχάρης Σταμάτιος, Καθηγητής, Ιατρικής Σχολής, ΕΚΠΑ
Καραμούζης Μιχάλης, Αν. Καθηγητής, Ιατρικής Σχολής, ΕΚΠΑ
Πιπέρη Χριστίνα, Αν. Καθηγήτρια, Ιατρικής Σχολής, ΕΚΠΑ
Ψυρρή Διαμάντω, Αν. Καθηγήτρια, Ιατρικής Σχολής, ΕΚΠΑ
Τρουπής Θεόδωρος, Αν. Καθηγητής, Ιατρικής Σχολής, ΕΚΠΑ
Σαέττα Αγγελική, Καθηγήτρια, Ιατρικής Σχολής, ΕΚΠΑ

H ενδοκυττάρια οδός μετακίνησης του egfr στον καρκίνο του παχέος εντέρου

Greek

The endocytic pathway of EGFR trafficking in colorectal cancer

Autophagy has been identified as a catabolic mechanism in cells but its' role in cancer remains controversial. Autophagy has been characterized either as tumor suppressor or inducer mechanism in many tumor types. Monoclonal antibodies against EGFR (cetuximab and panitumumab) represent a major step in the treatment of mCRC. Several studies propose that cetuximab and panitumumab trigger autophagy which reveals a potential resistance mechanism to these agents. The last few years immunotherapy appears to be a novel promising strategy for the treatment of patients with solid tumors, including colorectal cancer. Checkpoint inhibitors, such as anti-PD1 (Nivolumab and Pembrolizumab) and anti-CTLA-4 (Ipilimumab) antibodies have already been developed and applied in mCRC patients with MSI-H phenotype. The association between mtBRAF and autophagy or MSI status has already been characterized. In our study, we identify the autophagy initiation through anti-EGFR monoclonal antibodies and checkpoint inhibitors in colorectal carcinoma cell lines according to microsatellite status. The combination of autophagy inhibition, anti-EGFR antibodies and checkpoint inhibitors as well as autophagy targeting, MEK inhibition and anti-EGFR antibodies or checkpoint inhibitors appears to be the best treatment approach for microsatellite instability high and stable colorectal cancer cell lines, respectively. Both combinatorial approaches reduce cell viability through the induction of apoptotic cell death. The findings of this study point out the importance of different approach for the treatment of BRAF mutant metastatic colorectal cancers based on their microsatelite instability phenotype.

Medicine

Autophagy; Colorectal cancer; Immunotherapy

No

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No

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https://pergamos.lib.uoa.gr/uoa/dl/object/2898430