Maria J Bueno1, Jose L Ruiz-Sepulveda1, Miguel Quintela-Fandino2,3,4,5. 1. Breast Cancer Clinical Research Unit-Clinical Research Program, CNIO-Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029, Madrid, Spain. 2. Breast Cancer Clinical Research Unit-Clinical Research Program, CNIO-Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029, Madrid, Spain. mquintela@cnio.es. 3. Medical Oncology, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain. mquintela@cnio.es. 4. Medical Oncology, Hospital Universitario Quiron, Pozuelo de Alarcon, Madrid, Spain. mquintela@cnio.es. 5. Department of Medicine, Universidad Autonoma de Madrid, Madrid, Spain. mquintela@cnio.es.
Abstract
PURPOSE OF REVIEW: Mitochondria have a major impact on virtually all processes linked to oncogenesis. Thus, mitochondrial metabolism inhibition has emerged as a promising anticancer strategy. In this review, we discuss the anticancer potential of mitochondrial inhibitors, with particular focus on metformin, in the context of more effective, targeted therapeutic modalities, and diagnostic strategies for cancer patients. RECENT FINDINGS: Metformin has gained interest as an antitumor agent. However, promising results have not been translated into remarkable advances in the clinical practice. Recent findings emphasize the need of providing a metabolic context in which mitochondrial inhibitors may elicit its anticancerous effects. In addition, mitochondria are critical regulators in orchestrating immune responses. Thus, the immunomodulatory effect of mitochondrial inhibitors should also be taken into account to optimize its clinical use. Targeting mitochondrial metabolic network represents a promising therapeutic strategy in cancer. However, there is a need to define the metabolic context in which mitochondrial inhibitors are more effective, as well as how the cross-talk between many immunological functions and mitochondrial functionality may be exploited for a therapeutic benefit in cancer patients.
PURPOSE OF REVIEW: Mitochondria have a major impact on virtually all processes linked to oncogenesis. Thus, mitochondrial metabolism inhibition has emerged as a promising anticancer strategy. In this review, we discuss the anticancer potential of mitochondrial inhibitors, with particular focus on metformin, in the context of more effective, targeted therapeutic modalities, and diagnostic strategies for cancer patients. RECENT FINDINGS: Metformin has gained interest as an antitumor agent. However, promising results have not been translated into remarkable advances in the clinical practice. Recent findings emphasize the need of providing a metabolic context in which mitochondrial inhibitors may elicit its anticancerous effects. In addition, mitochondria are critical regulators in orchestrating immune responses. Thus, the immunomodulatory effect of mitochondrial inhibitors should also be taken into account to optimize its clinical use. Targeting mitochondrial metabolic network represents a promising therapeutic strategy in cancer. However, there is a need to define the metabolic context in which mitochondrial inhibitors are more effective, as well as how the cross-talk between many immunological functions and mitochondrial functionality may be exploited for a therapeutic benefit in cancer patients.
Entities:
Keywords:
Cancer therapy; Metabolic context; Mitochondrial inhibitors; Mitochondrial metabolism; immunotherapy
Authors: René Günther Feichtinger; Serge Weis; Johannes Adalbert Mayr; Franz Zimmermann; Reinhard Geilberger; Wolfgang Sperl; Barbara Kofler Journal: Glia Date: 2014-01-20 Impact factor: 7.452
Authors: Rene' G Feichtinger; Franz Zimmermann; Johannes A Mayr; Daniel Neureiter; Cornelia Hauser-Kronberger; Freimut H Schilling; Neil Jones; Wolfgang Sperl; Barbara Kofler Journal: BMC Cancer Date: 2010-04-19 Impact factor: 4.430
Authors: Johannes A Mayr; David Meierhofer; Franz Zimmermann; Rene Feichtinger; Christian Kögler; Manfred Ratschek; Nikolaus Schmeller; Wolfgang Sperl; Barbara Kofler Journal: Clin Cancer Res Date: 2008-04-15 Impact factor: 12.531
Authors: Yonathan Lissanu Deribe; Yuting Sun; Christopher Terranova; Fatima Khan; Juan Martinez-Ledesma; Jason Gay; Guang Gao; Robert A Mullinax; Tin Khor; Ningping Feng; Yu-Hsi Lin; Chia-Chin Wu; Claudia Reyes; Qian Peng; Frederick Robinson; Akira Inoue; Veena Kochat; Chang-Gong Liu; John M Asara; Cesar Moran; Florian Muller; Jing Wang; Bingliang Fang; Vali Papadimitrakopoulou; Ignacio I Wistuba; Kunal Rai; Joseph Marszalek; P Andrew Futreal Journal: Nat Med Date: 2018-06-11 Impact factor: 53.440