Metabolomic analysis reveals a key weakness in neuroblastoma: dependence on fatty acids for survival

The researchers were able to reduce the growth
of MYCN-amplified tumors.

"Treating neuroblastoma directly against MYCN is challenging," said
Eveline Barbieri, Ph.

Barbieri and her colleagues compared the metabolic profiles
of MYCN-ampened neuroblastomas with non-MYCN-amplified neuroblastomas using unbiased metabolomic analysis.

Barbieri said: "We found that the amplification of MYCN recombins the lipid metabolism of tumors, promoting the use and biosynthesis of fatty acids, a type
of lipid that lipid cells can use as a source of energy.

Barbieri and her colleagues propose that MYCN changes the route of lipid metabolism to make it easier for fatty acids to enter cancer cells, thereby promoting the growth
of tumor cells.

Study its mechanism

Barbieri said: "When we looked at what prompted MYCN-amplified neuroblastomas to grow fatty acid-dependent growth, we found that MYCN directly upregulates or enhances the production of fatty acid transporter 2 (FATP2), the molecule
that mediates cellular absorption of fatty acids.

When the researchers neutralized the activity of FATP2 by knocking out the gene or blocking the action of FATP2 with a small molecule inhibitor, they reduced the growth
of MYCN-amplified tumors.

Barbieri said: "We observed that when we block fatty acids from entering cancer cells, the growth of tumor cells decreases
.

There are other MYCN-amplified childhood and adult tumors
.

These findings suggest that therapeutic interventions that interfere with FATP2 activity may selectively block fatty acid uptake by MYCN-ampampled tumors, stopping or reducing tumor growth, making it more sensitive
to conventional chemotherapy.

Barbieri said: "More needs
to be done before this approach can be applied to the clinic.

MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma