Catastrophic ATP loss underlies a metabolic combination therapy tailored for MYCN-amplified neuroblastoma.

ABSTRACT: MYCN-amplified neuroblastoma is a lethal subset of pediatric cancer. MYCN drives numerous effects in the cell, including metabolic changes that are critical for oncogenesis. The understanding that both compensatory pathways and intrinsic redundancy in cell systems exists implies that the use of combination therapies for effective and durable responses is necessary. Additionally, the most effective targeted therapies exploit an "Achilles' heel" and are tailored to the genetics of the cancer under study. We performed an unbiased screen on select metabolic targeted therapy combinations and correlated sensitivity with over 20 subsets of cancer. We found that MYCN-amplified neuroblastoma is hypersensitive to the combination of an inhibitor of the lactate transporter MCT1, AZD3965,

SUBMITTER: Dalton KM 

PROVIDER: S-EPMC8020796 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature