Year: 2020
Type: article
Abstract: Cancer cells adjust their metabolic profiles to evade treatment. Metabolic adaptation is complex and hence better understood by an integrated theoretical-experimental approach. Using a minimal kinetic model, we predicted a previously undescribed Low/Low (L/L) phenotype, characterized by low oxidative phosphorylation (OXPHOS) and low glycolysis. Here, we report that L/L metabolism is observed in BRAF -mutated melanoma cells that enter a drug-tolerant “idling state” upon long-term MAPK inhibition (MAPKi). Consistently, using publicly available RNA-sequencing data of both cell lines and patient samples, we show that melanoma cells decrease their glycolysis and/or OXPHOS activity upon MAPKi and converge toward the L/L phenotype. L/L metabolism is unfavorable for tumor growth, yet supports successful cell division at ~50% rate. Thus, L/L drug-tolerant idling cells are a reservoir for accumulating mutations responsible for relapse, and it should be considered as a target subpopulation for improving MAPKi outcomes in melanoma treatment.
Source: Frontiers in Oncology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G1047773206, G1152932680, G227903998, G2314922425, Quantitative Multiscale Imaging to Optimize Cancer Treatment Strategies, G4600638491, G500871726, Phenotype Heterogeneity and Dynamics in SCLC, G5925180697, Center for Theoretical Biological Physics, G6398778466, Computational Cancer Biology Training Program, Center for Theoretical Biological Physics - Houston, G82375827, G8556403166, G9000021523, G9000023339, G9000118121, G9000164690, G9000254113, G930930142, G939774631
OpenAlex ID: W3048540934