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Identifier 000460149
Title Λογικοί συνδιασμοί αντικαρκινικών φαρμάκων
Alternative Title Rational combinations of anticancer drugs
Author Συντιχάκη Άννα-Μαρία
Thesis advisor Πίντζας, Αλέξανδρος
Reviewer Μήτσιου, Δήμητρα
Παπαδόδημα-Όλγα
Abstract The colorectal and breast are two examples of cancer with a high prevalence in the population. 15% of colorectal cancer cases possess the BRAFV600E mutation, thus making it an ideal therapeutic target. Unfortunately, inhibitors targeting the BRAFV600E have a limited effect on colorectal cancer, thus the efforts are turning towards the combinatorial targeting of the disease. Meanwhile, for the past few decades, tamoxifen has been used for targeting ERαα(+) breast cancer, while ERαα(-) remains a challenge. Nevertheless, resistance occurs often even in the ERαα(+) cancers that were originally responsive to tamoxifen. In the present study, the effects of the inhibitors that target the BRAFV600E mutation Encorafenib, Dabrafenib, PLX4720, PLX7904 and PLX8394 and the antiestrogen 4-hydroxytamoxifen were tested on the colorectal cancer cell lines HT-29, COLO-205 and RKO that possess the BRAFV600E mutation and on the breast cancer cell line MDA-MB-231 that possess the BRAFG464V. When tested individually, all of the inhibitors were found to effectively reduce the viability of the colorectal cell lines, alongside the reduction of the pERK levels, while being proven less effective at the MDA-MB-231 cells. Subsequently, rational combinations of the agents were used for each of the cell lines. In some cases, the combinations produced an additive effect compared to the monotreatments, while in the case of the combination of PLX7904 with 4-hydroxytamoxifen there was even a synergistic mode of action of the agents in the MDA-MB-231 cells. Furthermore, cell cycle analysis on the HΤΤ-29 cells showed that the inhibitors could affect the cell cycle when used in a monotreatment context while some of the combinatorial treatments could evoke significant changes in the cell cycle in relation to the monotreatments. The above data advocate for the need for further studying of the combinatorial treatments with the BRAF inhibitors and 4-hydroxytamoxifen, so that any potential synergistic actions may be identified.
Language Greek, English
Subject 4-Hydroxytamoxifen
4-υδροξυταμοξιφαίνη
BRAFV600E inhibitors
BRAFV600E αναστολείς
Issue date 2023-12-08
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/2/9/a/metadata-dlib-1701944596-955085-4303.tkl Bookmark and Share
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