The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma.

ABSTRACT:

Background

Neuroblastoma is a deadly childhood cancer, and MYCN-amplified neuroblastoma (MNA-NB) patients have the worst prognoses and are therapy-resistant. While retinoic acid (RA) is beneficial for some neuroblastoma patients, the cause of RA resistance is unknown. Thus, there remains a need for new therapies to treat neuroblastoma. Here we explored the possibility of combining a MYCN-specific antigene oligonucleotide BGA002 and RA as therapeutic approach to restore sensitivity to RA in NB.

Methods

By molecular and cellular biology techniques, we assessed the combined effect of the two compounds in NB cell lines and in a xenograft mouse model MNA-NB.

Results

We found that MYCN-specific inhibition by BGA002 in combination with RA (BGA002-RA) act synergistically and

SUBMITTER: Lampis S 

PROVIDER: S-EPMC9055702 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature