التفاصيل البيبلوغرافية
| العنوان: |
Metronomic Chemotherapy Modulates Clonal Interactions to Prevent Drug Resistance in Non-Small Cell Lung Cancer |
| المؤلفون: |
Maryna Bondarenko, Marion Le Grand, Yuval Shaked, Ziv Raviv, Guillemette Chapuisat, Cécile Carrère, Marie-Pierre Montero, Mailys Rossi, Eddy Pasquier, Manon Carré, Nicolas André |
| المصدر: |
Cancers; Volume 13; Issue 9; Pages: 2239 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2021 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
metronomic chemotherapy, intratumor heterogeneity, mathematical modeling, non-small cell lung cancer, glycolytic activity, lactate dehydrogenase |
| الوصف: |
Despite recent advances in deciphering cancer drug resistance mechanisms, relapse is a widely 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 2D and 3D non-small cell lung cancer co-culture systems and defined a phenomenological mathematical model to better understand clone dynamics. Our results demonstrated that the drug-sensitive clones inhibit the proliferation of the drug-resistant ones under untreated conditions. Model predictions and their experimental in vitro and in vivo validations indicated that a metronomic schedule leads to 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 -resistant clones exhibited different metabolic statuses that could be involved in controlling the intratumor heterogeneity dynamics. Our data suggested that the glycolytic activity of drug-sensitive clones could play a major role in inhibiting the drug-resistant clone proliferation. Altogether, these computational and experimental approaches provide foundations for using metronomic therapy to control drug-sensitive and -resistant clone balance and highlight the potential of targeting cell metabolism to manage intratumor heterogeneity. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
https://dx.doi.org/10.3390/cancers13092239Test |
| DOI: |
10.3390/cancers13092239 |
| الإتاحة: |
https://doi.org/10.3390/cancers13092239Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.9824FA9A |
| قاعدة البيانات: |
BASE |
