ALK mutation

Further studies revealed that CCN1 could affect the expression of VEGFA by affecting AKT phosphorylation, and the change of NF-κB could impact the activation of CCN1-AKT-VEGFA pathway. Suppressing NF-κB or CCN1 receptor could improve the sensitivity to alectinib, further suggesting that NF-κB and CCN1 might play a key role in overcoming reversible drug resistance.

The younger generation has fewer opportunities for radiography or computed tomography, and accidental detection during the examination of other diseases is extremely valuable and effective. Awareness-building activities for pediatricians and other specialists, such as general internal medicine specialists, are important for improving the outcomes of young patients with lung cancer.

Lung cancer primarily affects men, with a mean age at diagnosis similar to that reported in other studies. Smoking remains the main risk factor, while biomass exposure also contributes to risk in the region. Most patients were diagnosed at advanced stages of the disease. Adenocarcinoma was the most frequent subtype, with EGFR and ALK mutations found at lower rates than in other national studies. PDL-1 expression showed a significant association with bio-mass exposure and advanced stages of the disease.

Next-generation sequencing (NGS) performed on both lesions revealed the presence of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion mutations in both lesions. Notably, the patient achieved a significant therapeutic response to ALK-tyrosine kinase inhibitors (TKIs) targeted therapy..

P2, N=27, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

P=N/A, N=30, Not yet recruiting, Shapingba District People's Hospital, Chongqing; Shapingba District People's Hospital Affiliated with Chongqing University

P=N/A, N=53, Not yet recruiting, Shanghai Geriatric Medical Center; Shanghai Geriatric Medical Center

P=N/A, N=53, Not yet recruiting, Shanghai Chest Hospital; Shanghai Chest Hospital

P2, N=52, Not yet recruiting, Shanghai Chest Hospital; Shanghai Chest?Hospital

P2, N=40, Not yet recruiting, Liaoning Cancer Hospital & Institute; Liaoning Cancer Hospital & Institute

P=N/A, N=92, Recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P=N/A, N=30, Not yet recruiting, Henan Cancer Hospital; Henan Cancer Hospital

P=N/A, N=100, Not yet recruiting, Tianjin Medical University General Hospital; Tianjin Medical University General Hospital

P2, N=43, Completed, Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital Institute); Shandong First Medical University an

P=N/A, N=60, Not yet recruiting, Chongqing university cancer hospital; Chongqing university cancer hospital

P2, N=20, Recruiting, the Third Affiliated Hospital of Sun Yat sen University; the Third Affiliated Hospital of Sun Yat sen University

P1, N=32, Not yet recruiting, Henan Cancer Hospital; Henan Cancer Hospital

In comparison to single-target inhibitors, ALK dual inhibitors offer the benefits of reducing the emergence of drug resistance, improving treatment efficacy, and optimizing pharmacokinetic features due to the synergistic function of ALK and other associated targets involved in tumor progression. Therefore, we outline the development of ALK dual inhibitors, highlight their design approaches and structure-activity relationship (SAR), and offer insights into new challenges and potential future directions in this area.

Here, we analyzed molecular profiles of 108 alectinib-treated patients (first-line and second-line after crizotinib) with confirmed relapse by targeted sequencing of cancer-related genes. After second-line treatment, the most common mutations in v1 were L1196M (42%) and G1269A (25%), while G1202R was detected in 45% of v3 tumors. These findings emphasize the importance of stratifying resistance mechanisms to guide tailored treatment for ALK-positive NSCLCs.

This is the first report demonstrating the efficacy of brigatinib after alectinib failure in a patient with duodenal carcinoma harboring ALK fusion. Furthermore, this case suggests that ctDNA sequencing can detect specific acquired mutations and help expand optimal treatment options for patients.

The ALK-TKI may be a new treatment option for these patients. This article provides a therapeutic reference.

P=N/A, N=15, Recruiting, Amsterdam UMC, location VUmc | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2025 --> Jan 2027

P2, N=124, Recruiting, Shanghai Chest Hospital | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

Ontologies improve data quality by identifying inconsistencies, enhancing data completeness, facilitating complex SQL queries, and standardize processes. Developing a framework to manage inconsistent healthcare data, considering its temporal nature, is essential.

Precision treatment strategies targeting these molecular mechanisms have shown certain prospects in preclinical studies and clinical practice. This review focuses on the relevant mechanisms and molecular characteristics of relapsed/refractory neuroblastoma, explores its relationship with treatment response and clinical prognosis, and briefly introduces the current treatment strategies to provide a theoretical basis for the development of novel and personalized therapeutic regimens to improve the prognosis of children.

We point out that large cell neuroendocrine carcinoma complex patients with RET gene mutation can benefit from targeted therapy, and when drug resistance is accompanied by ALK comutation, the patient can benefit from the treatment of the aletinib combined with pilatinib targeted therapy and the side effect is slight. At the same time, we further explore the resistance mechanism of targeted therapy in lung cancer.

The presented combined model based on GPTV3 effectively mined tumor features to predict ALK mutation status and stratify PFS outcomes in patients with lung adenocarcinoma.

P1/2, N=56, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Dec 2024 --> Dec 2025

P1, N=22, Terminated, Coherus Biosciences, Inc. | Phase classification: P1/2 --> P1

P3, N=474, Recruiting, NRG Oncology | Trial completion date: Oct 2036 --> Oct 2031

P1, N=69, Recruiting, Bayer | N=102 --> 69 | Trial completion date: Mar 2027 --> Jul 2025 | Trial primary completion date: Mar 2027 --> Jul 2025

Ultra-deep sequencing of high-risk NBLs demonstrates that oncogenic aberrations are more prevalent at diagnosis than previously recognized. ALK and RAS pathway aberrations confer inferior outcomes in patients treated with contemporary therapy, emphasizing the need for novel therapeutic approaches.

ctDNA testing to detect oncogenic fusions or METexon14 mutations in advanced NSCLC patients is useful, even if type of gene alterations and clinical characteristics could influence the driver detection rate. Liquid biopsy represents a complementary tool to tissue genotyping, however more sensitive approaches for gene fusions and METexon14 detection are needed to implement its strength and reliability.

P1/2, N=242, Suspended, Roswell Park Cancer Institute | Recruiting --> Suspended

AO/EtBr differential staining revealed apoptotic phenomena in NB cells after 24 h of PPP treatment. Although further research is needed to explore the receptor targeting approach using PPP for IGF1R and ALK inhibition.

Due to the rarity of co-mutations, the case not only enriches the limited literature on NSCLC harbouring BRAF G469A and echinoderm microtubule associated protein like-4 mutations, but also suggests the efficacy and safety of specific multiple-drug therapy in such patients.

P1, N=115, Active, not recruiting, Daiichi Sankyo | Trial primary completion date: Dec 2024 --> Jul 2025 | Recruiting --> Active, not recruiting

The activation of downstream pathways and the response to ALK inhibitors crizotinib and alectinib were demonstrated by western blotting (WB). We identified and functionally validated PLCXD3-ALK as a novel rare fusion in NSCLC that has not been previously reported. It can serve as a meaningful therapeutic target for ALK inhibitors of ALK + NSCLC.

P1/2, N=5, Terminated, Genprex, Inc. | N=180 --> 5 | Trial completion date: Dec 2025 --> Feb 2025 | Active, not recruiting --> Terminated; Enrollment was slow, due to competition with the many other clinical trials for the same patient population, which led to the decision to end enrollment in the trial.

P1, N=65, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial primary completion date: Dec 2024 --> Dec 2025

The modeling simulation revealed that the G1202R mutation exerted little effect on the binding of iruplinalkib. Iruplinalkib showed potency to G1202R because of its unique chemical structure and removal of steric clashes, which might be a promising option for ALK-rearranged NSCLC patients with G1202R resistance mutation.

P2, N=13, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=40 --> 13