Reconciling environment-mediated metabolic heterogeneity with the oncogene-driven cancer paradigm in precision oncology.
Semin Cell Dev Biol
; 98: 202-210, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31103464
ABSTRACT
Precision oncology is the practice of matching one therapy to one specific patient, based on particular genetic tumor alterations, in order to achieve the best clinical response. Despite an expanding arsenal of targeted therapies, many patients still have a poor outcome because tumor cells show a remarkable capacity to develop drug resistance, thereby leading to tumor relapse. Besides genotype-driven resistance mechanisms, tumor microenvironment (TME) peculiarities strongly contribute to generate an intratumoral phenotypic heterogeneity that affects disease progression and treatment outcome. In this Review, we describe how TME-mediated metabolic heterogeneities actively participate to therapeutic failure. We report how a lactate-based metabolic symbiosis acts as a mechanism of adaptive resistance to targeted therapies and we describe the role of mitochondrial metabolism, in particular oxidative phosphorylation (OXPHOS), to support the growth and survival of therapy-resistant tumor cells in a variety of cancers. Finally, we detail potential metabolism-interfering therapeutic strategies aiming to eradicate OXPHOS-dependent relapse-sustaining malignant cells and we discuss relevant (pre)clinical models that may help integrate TME-driven metabolic heterogeneity in precision oncology.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oncogenes
/
Medicina de Precisión
/
Lactatos
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article