Lactic acid fermentation: A maladaptive mechanism and an evolutionary throwback boosting cancer drug resistance.
Biochimie
; 208: 180-185, 2023 May.
Article
em En
| MEDLINE
| ID: mdl-36638953
ABSTRACT
After four decades of research primarily focused on tumour genetics, the importance of metabolism in tumour biology is receiving renewed attention. Cancer cells undergo energy, biosynthetic and metabolic rewiring, which involves several pathways with a prevalent change from oxidative phosphorylation (OXPHOS) to lactic acid fermentation, known as the Warburg effect. During carcinogenesis, microenvironmental changes can trigger the transition from OXPHOS to lactic acid fermentation, an ancient form of energy supply, mimicking the behaviour of certain anaerobic unicellular organisms according to "atavistic" models of cancer. However, the role of this transition as a mechanism of cancer drug resistance is unclear. Here, we hypothesise that the metabolic rewiring of cancer cells to fermentation can be triggered, enhanced, and sustained by exposure to chronic or high-dose chemotherapy, thereby conferring resistance to drug therapy. We try to expand on the idea that metabolic reprogramming from OXPHOS to lactate fermentation in drug-resistant tumour cells occurs as a general phenotypic mechanism in any type of cancer, regardless of tumour cell heterogeneity, biodiversity, and genetic characteristics. This metabolic response may therefore represent a common feature in cancer biology that could be exploited for therapeutic purposes to overcome chemotherapy resistance, which is currently a major challenge in cancer treatment.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Láctico
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article