دورية أكاديمية
Metronomic Chemotherapy Modulates Clonal Interactions to Prevent Drug Resistance in Non-Small Cell Lung Cancer
| العنوان: | Metronomic Chemotherapy Modulates Clonal Interactions to Prevent Drug Resistance in Non-Small Cell Lung Cancer |
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| المؤلفون: | Bondarenko, Maryna, Le Grand, Marion, Shaked, Yuval, Raviv, Ziv, Chapuisat, Guillemette, Carrère, Cécile, Montero, Marie-Pierre, Rossi, Mailys, Pasquier, Eddy, Carré, Manon, André, Nicolas |
| المساهمون: | Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Assistance Publique - Hôpitaux de Marseille (APHM), Cell Biology and Cancer Science Haifa, Israel, Rappaport faculty of Medicine, Technion - Israel Institute of Technology Haifa -Technion - Israel Institute of Technology Haifa, Metronomics Global Health Initiative, Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Institut Denis Poisson (IDP), Université d'Orléans (UO)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie et d'Oncologie pédiatrique, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone CHU - APHM (TIMONE)-Metronomics Global Health Initiative, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 2072-6694. |
| بيانات النشر: | HAL CCSD MDPI |
| سنة النشر: | 2021 |
| المجموعة: | Université d'Orléans: HAL |
| مصطلحات موضوعية: | metronomic chemotherapy, Intratumor heterogeneity, mathematical modeling, non-small cell lung cancer, glycolytic activity, lactate dehydrogenase, [MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] |
| الوصف: | International audience ; :Despite recent advances in deciphering cancer drug resistance mechanisms, relapse is awidely observed phenomenon in advanced cancers, mainly due to intratumor clonal heterogeneity.How tumor clones progress and impact each other remains elusive. In this study, we developed 2Dand 3D non-small cell lung cancer co-culture systems and defined a phenomenological mathematicalmodel to better understand clone dynamics. Our results demonstrated that the drug-sensitive clonesinhibit the proliferation of the drug-resistant ones under untreated conditions. Model predictionsand their experimentalin vitroandin vivovalidations indicated that a metronomic schedule leadsto a better regulation of tumor cell heterogeneity over time than a maximum-tolerated dose schedule,while achieving control of tumor progression. We finally showed that drug-sensitive and -resistantclones exhibited different metabolic statuses that could be involved in controlling the intratumorheterogeneity dynamics. Our data suggested that the glycolytic activity of drug-sensitive clones couldplay a major role in inhibiting the drug-resistant clone proliferation. Altogether, these computationaland experimental approaches provide foundations for using metronomic therapy to control drug-sensitive and -resistant clone balance and highlight the potential of targeting cell metabolism tomanage intratumor heterogeneity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03267511; https://hal.science/hal-03267511Test; https://hal.science/hal-03267511/documentTest; https://hal.science/hal-03267511/file/Metronomic_Chemotherapy_Cancers.pdfTest |
| DOI: | 10.3390/cancers13092239 |
| الإتاحة: | https://doi.org/10.3390/cancers13092239Test https://hal.science/hal-03267511Test https://hal.science/hal-03267511/documentTest https://hal.science/hal-03267511/file/Metronomic_Chemotherapy_Cancers.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.43C0F82A |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cancers13092239 |
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