Abstract 4317: The role of autophagy in triple negative breast cancer

Abstract Breast cancer (BC) remains a global health concern, being the most common cancer amongst women in the world, and the second-leading cause of cancer related death. Triple-negative breast cancer (TNBC) represents a challenging frontier in oncology, characterized by its aggressiveness and its...

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Published inCancer research (Chicago, Ill.) Vol. 84; no. 6_Supplement; p. 4317
Main Authors Gamal, Sameh, El-Nikhely, Nefertiti A., Nematallah, Hesham, Saeed, Hesham M.
Format Journal Article
LanguageEnglish
Published 22.03.2024
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Summary:Abstract Breast cancer (BC) remains a global health concern, being the most common cancer amongst women in the world, and the second-leading cause of cancer related death. Triple-negative breast cancer (TNBC) represents a challenging frontier in oncology, characterized by its aggressiveness and its unique molecular profile devoid of the known receptors. Its elusiveness lies in the inherent heterogeneity within its subtypes, contributing to diverse clinical behaviours and treatment responses. TNBC has also shown elevated basal autophagy level as a pro-survival mechanism to make up for the increased nutrients demand mandated by the high K-RAS signalling. To tackle such tumour, we chose an autophagy blocker in addition to multi-kinase inhibitor. The combination index calculated for the proposed drugs has shown promising results in reduction of cell viability more than each drug separately. Selectivity index proved the safety of our doses on normal fibroblast cells in contrast to two breast cancer cell lines (MDA-MB 231 & MCF7). To further complement the findings, cell cycle arrest was witnessed at S phase which lead to apoptosis seen by flowcytometry and other expression analysis studies. Finally, Imaging studies and expression analysis on protein level have documented the apoptotic effects rendered by autophagy inhibition.Research endeavours continue to unravel the intricate landscape of TNBC, seeking novel avenues for targeted treatments, immunotherapies, and personalized medicine, aiming to transform the paradigm of care for those affected by this enigmatic form of breast cancer. As evident from the results, our combination has also managed to reduce the cells migration effectively which reflects that it can be initiated with aggressive metastatic tumours like TNBC. Citation Format: Sameh Gamal, Nefertiti A. El-Nikhely, Hesham Nematallah, Hesham M. Saeed. The role of autophagy in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4317.
ISSN:1538-7445
1538-7445
DOI:10.1158/1538-7445.AM2024-4317