Can loratinib break the dilemma of ALK mutant neuroblastoma treatment?

Article source: Med

Author: Ala Lei

Lolatinib, the third-generation ALK inhibitor, has attracted attention in the field for its excellent performance in the treatment of NSCLC

Picture from: N Engl J Med.

Since it is a sharp sword, how can it better reflect its value? Naturally, it is to challenge a problem that others cannot solve

NB and ALK mutations

Neuroblastoma (NB) is the most common extracranial solid tumor in children, accounting for 8%-10% of childhood malignant tumors and 15% of childhood tumor-related deaths.

Studies have shown that about 6% to 10% of NBs have ALK mutations, making ALK inhibitors a possible treatment strategy

Picture from: Cancer (Basel).

However, the sensitivity of the first generation ALK inhibitor crizotinib to ALK mutant NB is not ideal

Clinical study of ALK inhibitor in NB

At present, there are few clinical research data on the correlation between ALK mutation characteristics and the efficacy of ALK inhibitors in NB

In May 2013, preliminary data was published in the journal Lancet Oncol.

As the third-generation ALK inhibitor, loratinib has shown anti-tumor activity against F1174, F1245, and R1275 in preclinical studies

There is also a case report from Cold Spring Harb

E map (maximum signal projection, MIP) and F map (SPECT/CT): disease recurrence period; G map (MIP) and H map (SPECT/CT): CR after the use of loratinib

However, drug resistance after loratinib treatment is also a problem that doctors must face

In the study of ALK-positive lung cancer, mutations related to loratinib resistance include: TP53, NRAS, BRCA1/2, APC, MAP3K1, BRAF, etc.

Overview of loratinib resistance mechanism.

Summary: According to the ALK mutation characteristics of NB, loratinib has more therapeutic potential than crizotinib

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