Research Progress in the Efficacy and Safety of ALK Inhibitors in the Treatment of NSCLC Brain Metastasis / 中国肺癌杂志

Lung cancer is one of the most lethal malignancies in the world, with non-small cell lung cancer (NSCLC) accounting for approximately 80%-85% of all pathological types. Approximately 30%-55% of NSCLC patients develop brain metastases. It has been reported that 5%-6% of patients with brain metastases harbor anaplastic lymphoma kinase (ALK) fusion. ALK-positive NSCLC patients have shown significant therapeutic benefits after treatment with ALK inhibitors. Over the past decade, ALK inhibitors have rapidly evolved and now exist in three generations: first-generation drugs such as Crizotinib; second-generation drugs including Alectinib, Brigatinib, Ceritinib, and Ensartinib; and third-generation drugs like Lorlatinib. These drugs have exhibited varying efficacy in treating brain metastases in ALK-positive NSCLC patients. However, the numerous options available for ALK inhibition present a challenge for clinical decision-making. Therefore, this review aims to provide clinical guidance by summarizing the efficacy and safety of ALK inhibitors in treating NSCLC brain metastases.
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Ceritinib as First-line Treatment for Advanced Lung Adenocarcinoma with COX7A2L-ALK Fusion: A Case Report and Literature Review / 中国肺癌杂志

Lung cancer is the most common in incidence and mortality worldwide. With the development of next generation sequencing (NGS) detection technology, more and more patients with rare anaplastic lymphoma kinase (ALK) fusion mutations were detected. A case of advanced lung adenocarcinoma with rare COX7A2L-ALK (C2:A20) fusion detected by NGS was reported in Peking Union Medical College Hospital, and all cases with rare ALK fusion mutations were searched from medical datebase from January 1, 2014 to March 31, 2021, to investigate the treatment of rare ALK fusion mutations with ALK inhibitors. The best response of the patient was assessed as partial response (PR) with Ceritinib treatment. By literature review, 22 cases of rare ALK fusion were reported in 19 articles. Combined with this case, 23 cases were analyzed. The objective response rate (ORR) was 82.6% (19/23) and disease control rate (DCR) was 95.7% (22/23) for rare ALK fusions patients treated with ALK inhibitors. Lung adenocarcinoma patients with rare ALK fusion could benefit from ALK inhibitors.
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Research progress of the resistance mechanism and reversal strategies of ALK inhibitors in NSCLC / 中国药科大学学报

@#Anaplastic lymphoma kinase (ALK) inhibitors are regarded as effective drugs for the treatment of ALK-positive NSCLC. However,the emergence of drug resistance has limited its further clinical application. This article briefly introduces the resistance mechanism of ALK inhibitors including acquired secondary mutations,gene amplification,bypass signaling pathway activation and reviews the recent advances on the reversal strategies such as drug combination,developing novel PROTACs to overcome drug resistance,so as to provide some reference for the development of ALK inhibitors.

Advances in Drug Resistance Mechanisms and Prognostic Markers of Targeted Therapy in ALK-positive Non-small Cell Lung Cancer / 中国肺癌杂志

Echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion accounts for 3%-5% of non-small cell lung cancer (NSCLC) patients. With the in-depth study of the EML4-ALK driver gene, ALK inhibitors represented by crizotinib have been gradually developed and applied in the clinic. However, the response to ALK-targeted therapy is heterogeneous among different patients. Most patients with ALK-targeted therapy will inevitably develop drug resistance, leading to tumor progression. Monitoring the efficacy of patients with prognostic markers to change the treatment in time, and selecting individualized follow-up treatment according to the mechanism of drug resistance, can effectively improve the prognosis of patients. This article will review the mechanism of ALK tyrosine kinase inhibitor (ALK-TKI) resistance and related prognostic markers to discuss the prediction for ALK-targeted therapy and the choice of subsequent treatment for drug-resistant patients.
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Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion

The World Health Organization 2016 edition assigned anaplastic lymphoma kinase (ALK) rearrangement-associated renal cell carcinoma (ALK-RCC) as an emerging renal tumor entity. Identifying ALK-RCC is important because ALK inhibitors have been shown to be effective in treatment. Here, we report the case of a 14-year-old young man with ALK-RCC. Computed tomography revealed a well-demarcated 5.3-cm enhancing mass at the upper pole of the left kidney. There was no further history or symptoms of the sickle-cell trait. The patient underwent left radical nephrectomy. Pathologically, the mass was diagnosed as an unclassified RCC. Targeted next-generation sequencing identified a TPM3-ALK fusion gene. The present report and literature review demonstrate that TPM3-ALK RCC may be associated with distinct clinicopathological features. Microscopically, the tumors showed diffuse growth and tubulocystic changes with inflammatory cell infiltration. Tumor cells were dis-cohesive and epithelioid with abundant eosinophilic cytoplasm and cytoplasmic vacuoles. If morphological features and TFE3 expression are present in adolescent and young patients, molecular tests for ALK translocation should be performed. This awareness is critically important, because ALK rearrangement confers sensitivity to ALK inhibitors.

Research progress of positive ALK fusion gene non-small cell lung cancer / 解放军医学杂志

Lung cancer is the highest incidence of malignant tumor in the world, and is the leading cause of cancer death; 80%-85% of lung cancer is non-small cell lung cancer (NSCLC) and the positive rate of anaplastic lymphoma kinase (ALK) fusion gene in NSCLC patients is about 3%-7%. In recent years, targeted therapeutic drugs for ALK fusion gene have developed rapidly. The clinical use of ALK inhibitors such as clozotinib, aletinib and loratinib has significantly improved the survival of patients with ALK positive advanced NSCLC. However, the effect of ALK fusion gene positive on the prognosis of early NSCLC patients is not clear, and whether it can benefit from ALK inhibitor treatment is still unknown. The action mechanism of ALK fusion gene, the clinicopathologic features, the method of detection, the effect of ALK fusion gene positive on the prognosis of NSCLC patients and the recent progress of the ALK inhibitor are briefly described in present paper with a view to having a certain reference to the clinical work.