ALK fusion

The HEATR5B-ALK fusion is targetable by ensartinib, producing durable disease control and excellent tolerability. Comprehensive NGS and ALK IHC are essential for detecting rare actionable ALK variants.

Due to rapid enrollment, the target sample size was expanded to 28 patients. The primary endpoint is objective response rate confirmed by central assessment; secondary endpoints include duration of response, progression-free survival, overall survival, and safety.Clinical trial registration: jRCT2041210148 (https://jrct.mhlw.go.jp).

Therapy-induced cancer dormancy was mainly attributed to activation of unfolded protein response, specifically the PERK-eIF2α axis, which triggers cholesterol biosynthesis and AKT signaling. Collectively, this work uncovers an unexpected role of a therapy-induced prosurvival program in promoting cancer dormancy and provides a potentially effective strategy to prevent drug resistance.

In this study, there was no significant difference in the therapeutic effect of alectinib by ALK fusion variants. This finding indicates that alectinib may be an effective treatment option even for patients with V3.

Further analysis showed immunohistochemical ALK positivity, and Archer-based molecular testing identified a KLC1-ALK fusion (KLC1 exon 3-ALK exon 20). These findings supported the diagnosis of a cutaneous non-neural granular cell tumor, a rare cutaneous neoplasm that mimics conventional granular cell tumors histomorphologically but lacks their typical immunophenotype and commonly harbors ALK fusions.

The patient received two cycles of nab-paclitaxel and carboplatin, and repeated CT scan showed disease progression. Her treatment was subsequently changed to glumetinib plus iruplinalkib and she died less than one month later...Co-amplification of the multiple genes may be involved in aggressive disease and drug resistance, which should be considered in future clinical trials and clinical management. Early broad-panel next-generation sequencing testing in LUSCC patients who are never-smokers may help guide management for patients who have complex mutational profiles.

The study underscores the importance of integrating NGS-based molecular testing with PD-L1 evaluation for personalised management of NSCLC. Distinct patterns of PD-L1 expression across molecular subtypes, particularly lower in EGFR-mutated tumours and higher in KRAS-mutated tumours, underscore the need for tailored therapeutic strategies and informed sequencing of targeted therapies and immunotherapies.

These findings demonstrate that IHC-based screening followed by confirmatory FISH provides a rapid and cost-effective strategy for identifying cases of non-LCH with JXG morphology harboring actionable kinase alterations. Integration of IHC, FISH, and NGS represents a practical and complementary diagnostic strategy to guide precision therapy in this clinically diverse histiocytic disorder.

Subgroup analysis showed that the adverse effect of V3 was more pronounced in patients treated with crizotinib (HR = 1.40, 95%CI: 1.00-1.96, p=0.049), in the first line treatment setting (HR = 1.83, 95%CI: 1.34-2.50, p<0.001), and in those assessed by NGS (HR = 1.67, 95%CI: 1.34-2.08, p<0.001). A significant association was also observed in the brigatinib-treated population (HR = 2.09, 95%CI: 1.33-3.28, p=0.001), although this finding was based on only two studies...Prospective studies with standardized molecular subtyping are still needed before considering clinical stratification based on ALK variant types. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251229641, identifier CRD420251229641.

Following a second surgical resection and adjuvant radiation therapy, the patient was started on adjuvant targeted therapy with lorlatinib, an ALK kinase inhibitor. This report illustrates the role of immunotherapy and targeted therapy in melanoma treatment.

P1/2, N=11, Active, not recruiting, Hoffmann-La Roche | Phase classification: P3 --> P1/2 | Trial completion date: Mar 2033 --> Aug 2026 | Trial primary completion date: Jun 2028 --> Aug 2026