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Anaplastic lymphoma kinase (ALK) fusion was found in 3–7% of all patients with nonsmall cell lung cancer. The efficacy of ALK-tyrosine kinase inhibitor (ALK-TKI) in EML4-ALK has been extensively studied, whereas little evidence is available on its efficacy in rare ALK fusions. Here, we report the performance of crizotinib in a 50-year-old male lung adenocarcinoma patient with a novel rare SEC31A-ALK fusion. Computed tomography (CT) scan revealed multiple patchy high-density shadows in both lungs. The larger ones are located near the spine in the right lung lower lobe (55 × 34 mm) and the left hilar region (45 × 26 mm), with multiple enlarged mediastinal and axillary lymph nodes. Biopsy by bronchoscopy revealed invasive adenocarcinoma. The pathological stage of T4N3M1b (clinical stage: IVA) was confirmed. Next-generation sequencing revealed SEC31A: exon20~ALK: exon20 fusion, ABCB1 amplification, FGF19 amplification, DAXX p.S213L, MUTYH p.R19*(germline mutation and pathogenic) with tumor mutational burden at 3.2 mutations/Mb, microsatellite stable, proficient mismatch repair and PD-L1 positive [immunohistochemistry, tumor proportion score(TPS) 1–49% (TPS = 25%)]. Based on these findings, crizotinib was recommended for the first-line treatment at 250 mg twice daily. The first CT assessment after 2-month therapy showed partial response (PR) for the two larger lesions, multiple shadows and nodules in both lungs and the mediastinal and axillary lymph nodes. Crizotinib at 250 mg twice a day was applied in the following 9 months. Assessment at every 3 months (up to 1-year after diagnosis) showed further absorption for all lesions (continuous PR). We reported a novel rare ALK fusion SEC31A: EXON20~ALK: exon20 and showed the effectiveness of crizotinib against the fusion. This study provided strong evidence for the efficacy of ALK-TKI for rare ALK fusion.

Lipid raft-specific glycosylation has been implicated in many biological processes, including intracellular trafficking, cell adhesion, signal transduction, and host–pathogen interactions. The major predicament in lipid raft-specific glycosylation research is the unavailability of tools for tracking and manipulating glycans on lipid rafts at the microstructural level. To overcome this challenge, we developed a multifunctional proximity labeling (MPL) platform that relies on cholera toxin B subunit to localize horseradish peroxidase on lipid rafts. In addition to the prevailing electron-rich amino acids, modified sialic acid was included in the horseradish peroxidase-mediated proximity labeling substrate via purposefully designed chemical transformation reactions. In combination with sialic acid editing, the self-renewal of lipid raft-specific sialic acid was visualized. The MPL method enabled tracking of lipid raft dynamics under methyl-β-cyclodextrin and mevinolin treatments; in particular, the alteration of lipid rafts markedly affected cell migration. Furthermore, we embedded functional molecules into the method and implemented raft-specific sialic acid gradient engineering. Our novel strategy presents opportunities for tailoring lipid raft-specific sialic acids, thereby regulating interactions associated with lipid raft regions (such as cell–virus and cell–microenvironment interactions), and can aid in the development of lipid raft-based therapeutic regimens for tumors.