[Establishment of pediatric neuroblastoma cell line and its resistance mechanism to lorlatinib].

Neuroblastoma is a type of cancer that primarily affects children. In some cases, the tumor is driven by a genetic mutation in a protein called ALK, and doctors use a targeted drug named lorlatinib to stop it. Unfortunately, the cancer often learns to outsmart the treatment. To understand how this happens, scientists recently established a novel cancer cell line, named PUMC-NB1, from a pediatric patient's tumor. These lab-grown cells carry a specific ALK mutation, giving researchers a realistic model to study the disease.

By pushing these cells to develop resistance to the drug, the research team discovered the cancer's clever backup plan. When lorlatinib blocks the ALK protein, the tumor relies on a completely different protein called EGFR to survive. The cancer cells ramp up their production and activation of EGFR, creating a molecular detour that allows them to keep growing even when their main pathway is shut down.

The scientists then tested a way to block this escape route. They found that combining lorlatinib with afatinib, a drug that specifically inhibits EGFR, synergistically halted the growth of the resistant cancer cells. However, these findings are still in the early preclinical stages. The experiments were limited to cells in a lab dish and a small-scale trial involving five mice, meaning clinical trials are still needed to confirm if this two-drug combination is safe and effective for human patients.