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Deciphering mechanisms of cancer adaptation to targeted therapy
Sounni, Nor Eddine
2015Joint Symposium of University of Liege and Kobe University
 

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Keywords :
Cancer metabolism; targeted therapy; Drug resistance
Abstract :
[en] Targeted therapies designed towards specific molecules such as the receptor tyrosine kinase inhibitors (TKRIs) emerged in recent years and are currently in clinical use for multiple tumor types. Unfortunately, their efficacy is limited, in part due to the development of resistance to treatment. The first part of my talk will be focused on mechanisms of adaptation to antiangiogenic therapy using RTKIs in preclinical studies. Our recent data suggest that RTKIs withdrawal results in accelerated tumor progression and metastasis. We found that antiangiogenic therapy induced a metabolic shift in cancer and stromal cells to a glycolytic and hypoxic state during treatment, which was reversed upon therapy withdrawal, resulting in a shift to de novo lipogenesis and increased TCA cycle activity to promote tumor regrowth. Targeting lipid metabolism using pharmacological inhibition or specific knockdown of FASN suppressed the RTKIs withdrawal–associated tumor regrowth and metastasis. The second part of my talk will shed light on EGFR signaling in triple negative breast carcinomas (TNBC) and difficulties in targeting EGFR signaling. Although anti-EGFR treatments have shown promise in some cancers, single agent therapy is ineffective in unselected TNBC and response of patients is often limited due to the acquisition of resistance. Accumulating data have appreciated the importance of the cooperation of EGFR with other cell surface proteins to induce cell transformation, growth and survival. In this context, we recently reported that MT4-MMP, a membrane-type matrix metalloproteinase (MMP17) interacts with EGFR and enhances EGFR signaling and TNBC cell proliferation. I will also talk about our preclinical models and the opportunity to identify novel potential combination of treatment regimens that would increase the clinical benefit of targeted therapy against VEGF and EGFR.
Research center :
Giga-Cancer - ULiège
Disciplines :
Oncology
Author, co-author :
Sounni, Nor Eddine  ;  Université de Liège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Language :
English
Title :
Deciphering mechanisms of cancer adaptation to targeted therapy
Alternative titles :
[fr] Dechiffrer les mécanismes d'adaptation du cancer à la thérapie ciblée
Publication date :
12 May 2015
Number of pages :
1
Event name :
Joint Symposium of University of Liege and Kobe University
Event organizer :
University of Kobe, Japan
Event place :
Kobe, Japan
Event date :
12 mai 2015
Audience :
International
Funders :
ULg FSR - Université de Liège. Fonds spéciaux pour la recherche [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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since 05 January 2016

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