ALK rearrangement

P2, N=54, Recruiting, Shanghai Pulmonary Hospital, Shanghai, China

After 3 months, targeted lesions regressed significantly, and progression-free survival exceeded 24 months with ongoing response. This demonstrates efficacy of the ALK inhibitor ceritinib in ALK-rearranged SMARCA4-dNSCLC and underscores the clinical value of genomic-guided therapy.

While routine inflammation markers showed limited utility in predicting site-specific metastasis, LDH levels correlated significantly with liver involvement. Aggressive management strategies are warranted for ALK-positive patients presenting with liver metastases.

In non-small cell lung cancer (NSCLC), ALK gene rearrangements represent key oncogenic drivers, and ALK tyrosine kinase inhibitors (TKIs) such as crizotinib have significantly improved clinical outcomes...DATA AVAILABILITY: The raw RNA-seq reads and the processed gene expression matrix were deposited to the gene expression omnibus (accession number GSE284648). The data generated in this study are available from the author upon reasonable request.

The patient received first-line osimertinib combined with pemetrexed/cisplatin, achieving durable disease control for 17 months...Treatment was switched to alectinib, leading to significant tumor regression and partial response. This case illustrates that in triple-positive NSCLC, initial EGFR-TKI combined with chemotherapy can achieve long-term control, while dynamic molecular profiling at progression is essential for identifying resistance mechanisms. Sequential targeted therapy guided by NGS remains a cornerstone for precision management in this complex molecular subtype.

This case demonstrates an exceptionally durable response to first-line alectinib in an ALK-positive LUAD patient with a concurrent rare RET variant. It underscores the long-term efficacy and tolerability of alectinib and highlights the importance of comprehensive genomic profiling in guiding personalized targeted therapy for genetically complex NSCLC.

Our findings indicate that ALK-rearranged mesenchymal neoplasms with fibrosarcoma-like features, particularly those associated with elevated mitotic activity or tumor necrosis, should be classified as high grade in pathology reports. In addition, this case also demonstrated that neoadjuvant therapy may be a better treatment strategy compared to upfront surgery for ALK-rearranged mesenchymal neoplasms with a relatively high tumor burden.

Regimens co-targeting the MAPK pathway and ALK or ROS1 had limited efficacy in unselected patients with lorlatinib-resistant NSCLC, underscoring the need for more effective and biomarker-informed treatment strategies.

Since the approval of crizotinib, several next-generation ALK inhibitors have been introduced, offering improved treatment outcomes. The phase III eXalt3 study, a global randomized open-label trial, compared the efficacy of ensartinib, a second-generation ALK inhibitor, with crizotinib in patients with advanced ALK-rearranged NSCLC who had not received prior ALK-targeted therapy. With superior systemic and intracranial efficacy, ensartinib stands as a promising option in precision oncology. Ongoing research into improved ALK inhibitors and novel therapeutic strategies, including immune-based approaches, is expected to further improve patient outcomes.

P2, N=80, Recruiting, Stanford University | Trial primary completion date: Dec 2025 --> Dec 2026

ALK overexpression by immunohistochemistry and confirmatory molecular testing, when necessary, plays a critical diagnostic role. The expanding spectrum of ALK-rearranged cutaneous tumors underscores the value of an integrated diagnostic approach to ensure accurate diagnosis and guide clinical management.

PRMT5 inhibitor activity is independent of TKI exposure, driver alteration, and SDMA expression and enhanced by addition of TKI. These findings support clinical evaluation of PRMT5 inhibitor + TKI combinations for advanced NSCLC.