ALK mutation

Combining cases from our oncology center and previous literature, we found that NSCLC patients with coexisting ALK fusion mutations and other mutations have poorer response to targeted therapy and poorer prognosis, and we also compared the efficacy rates of various types of coexisting mutations for different treatment regimens. Therefore, this review can help to evaluate the prognosis of NSCLC patients with coexisting mutations and the efficacy of targeted therapies and to find more favorable treatment options for patients with this type of coexisting mutations.

EGFR mutations, especially rare variants (G724A, L747P, Q701 L, G719C, V769 L and S768I), exhibited significant enrichment in the non-AM group (P<0.001)...Meanwhile, patients with adrenal metastases harboring ALK or KRAS mutations have a poor prognosis and require more aggressive treatment. The TNF and TGF-β pathways might be associated with adrenal metastasis.

We evaluated crizotinib or 2nd generation ALK-TKI effectiveness in first-line treatment and lorlatinib in subsequent lines. This comprehensive study, spanning over a decade, provides crucial insights into the clinical characteristics, treatment patterns, and resistance mechanisms of advanced ALK-positive NSCLC, where median OS exceeds 5 years. Re-biopsies during treatment are essential for advancing our understanding of resistance mechanisms and the tumor dynamics evolving during ALK-TKI therapy.

The lack of association between molecular alteration status and recurrence risk prevailed after multivariable adjustment for tumor stage and perioperative treatment (P=0.82 for KRAS G12C mutation and P=0.43 for any other molecular alteration). NSCLC patients with resected tumors that harbor molecular alterations have the same recurrence risk as patients with tumors without molecular alterations if treated with surgery plus chemotherapy when indicated.

This study is the largest clinical study to date utilizing the TSO 500. It provides an opportunity to further characterize the landscape of NSCLC using this newer technology and show its clinical utility in detecting known and novel facets of NSCLC to inform treatment decision-making.

Furthermore, evaluations conducted in animal models have demonstrated that this drug effectively reduces tumor growth in vivo. In summary, (-)-9a boasts dual-targeting, potent antitumor activity, and immune-enhancing potential, presenting vast potential as a next-gen anticancer drug.

This real-world data analysis demonstrated that targeted therapies improve the survival of patients with NSCLC with actionable mutations, which supports a recommendation for widening access to broad-based genomic testing and targeted therapies.

Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.

Between January 2020 and February 2024, we identified four patients with either EML4-ALK fusions (2/4) or EGFR mutations (2/4) who underwent treatment with brigatinib or osimertinib before surgery. This case series highlights the potential of targeted therapies for resectable NSCLC in the neoadjuvant setting. Further research is required to confirm their benefits, assess their safety and efficacy, and determine optimal timing and sequencing.

After a minimum follow-up of 5 years, final analyses from the global phase 2 study confirmed substantial activity, prolonged OS, and generally consistent safety findings with lorlatinib in treatment-naïve and previously treated patients with ALK-positive NSCLC.

We used a gelatin- and silk fibroin-based hydrogel system with cross-linked vitronectin (VN) as an artificial biomimetic three-dimensional (3D) environment to mirror aggressive neuroblastoma (NB) tumors and tested long-term cell response to Cilengitide (CLG)...Cell detachment and aggregation were maintained in hydrogel-free monolayer cells whereas cells embedded in hydrogels presented different responses to treatment, suggesting differential anoikis resistance between the two cell lines. This underscores the advantages of testing therapeutic approaches using real-time imaging of tumor cells in 3D biomimetic models and its contribution to precision medicine.

Here we report a case of a 71 year-old man with metastatic pulmonary IMT harboring a DCTN1::ALK fusion that progressed during alectinib TKI treatment...To our knowledge, this is the first report of acquired p. V1180L mutation in IMTs treated with TKIs. In cases of ALK-positive IMTs that progress on TKI therapy, targeted sequencing for acquired ALK mutations may inform clinical decisions to adopt second-line therapeutic strategies.

As it is well-known that ALK-fusion and BRAF-mutations are described forms of acquired resistance. These two case reports contribute to the previous reports that ALK-fusion and BRAF-mutation are potential underlying mechanisms of EGFR-TKI resistance.

P1/2, N=316, Recruiting, Simcha IL-18, Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

The predictive model composed of these features or combined with sex and smoking habits exhibited statistically significant differences for mutation status as a criterion (P<0.01). Collectively, the findings of the present study confirmed that, in addition to clinical characteristics, certain cytological and histological features of lung adenocarcinoma are associated with the mutational status of the tumor.

In this particular case, treatment with crizotinib demonstrated some initial efficacy, which suggests that this might be a promising strategy for patients with advanced MPM with an ALK gene mutation. This required further research and evaluation in the future.

P1, N=169, Completed, Astellas Pharma Global Development, Inc. | Phase classification: P1b --> P1

P=N/A, N=100, Completed, Chongqing University Three Gorges Hospital（Chongqing Three Gorges Central Hospital）; Chongqing University Three Gorges Hospital（Chongqing Three

P4, N=100, Not yet recruiting, Anhui Chest Hospital; Anhui Chest Hospital

P1/2, N=540, Not yet recruiting, Shanghai East Hospital; CSPC Megalith Biopharmaceutical Co., Ltd.

All first-line treatments applied pembrolizumab (median dose: 12 cycles)...Of the patients with PRs or CRs, 75% were treated with platinum plus pemetrexed...The current response to second-line platinum-based therapies for patients with advanced NSCLC after immunotherapy appears to achieve favourable response rates and be an optimal treatment after progression to immunotherapy. Prior immunotherapy appears to enhance these patients' platinum response, though future confirmatory studies are necessary.

We have therefore identified a number of case series and phase II trials using targeted therapy in resectable EGFR-mutant and ALK-fused NSCLC. Current evidence suggests that targeted therapies might be effective in patients with resectable EGFR-mutant and ALK-positive NSCLC, but ongoing trials will need to provide further evidence on the safety and efficacy of perioperative TKI therapy.

This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases.

No abstract available

NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.

Finally, intravenous injection of CIGB-300 in a cell line-based xenograft corroborated CIGB-300's anti-tumor effects and suggested concurrent in situ reductions of CSNK2ɑ subunit and downstream RPS6s235/236 phosphorylation. Overall, CIGB-300 therapeutic hypothesis and antineoplastic effects demonstrated herein, further support the evaluation of this clinical-grade CK2 inhibitor in advanced NSCLC with limited therapeutic options.

Patients with ALK mutant, BRAF mutant or NRAS mutant were more prone to metastasis, while the HER 2 mutation group was less metastatic. Patients with EGFR mutant NSCLC are more likely to develop bone, lung, or brain metastasis.

Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS...After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

Dose adjustment due to AEs occurred in 17.9% of patients. Anlotinib combined with WBRT is effective and well-tolerated in patients with NSCLC with multiple BMs.

After the initial treatment with ensartinib, the patient experienced intracranial disease progression...Subsequent thoracic RT resulted in a partial response of the primary tumor; however, new brain and bone metastases were detected, prompting a switch to lorlatinib...Despite pembrolizumab treatment, the patient's condition deteriorated, and she passed away...Our findings revealed heterogeneity in ALK mutations and responses to ALK-TKIs, necessitating the close monitoring of genetic subtypes and associated mutations for tailored treatment strategies. Maintaining a heightened awareness of potential intestinal metastasis and vigilance in monitoring intestinal symptoms and abdominal metastases are pivotal for managing advanced lung adenocarcinoma.

Pulmonary sarcomatoid carcinoma (PSC) is a rare disease with strong aggressiveness, low response rates to treatment, short survival span and poor prognosis, belonging to a group of non-small cell lung carcinomas (NSCLC) that remains incompletely understood. Here, we presented three PSC cases with epidermal growth factor receptor (EGFR) L858R, BRAF V600E and ALK mutations respectively, described their clinical characteristics and conducted a review of literature, in order to improve its therapeutic level, which also provided evidence-based medical evidence for driver gene screening and molecular targeted drug application in PSC patients.

The tight binding of TPX-0131 to residues Arg1202, Met1199 and Arg1120 contribute significantly to overcoming lorlatinib resistance in ALKL1196M/G1202R mutant. These research results are expected to offer insights into the mechanism of TPX-0131 in treating ALKG1202R/L1196M-induced NSCLC resistance and optimizing of ALK inhibitors.

P2, N=40, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

Administration in combination with PPIs, amlodipine, and magnesium oxide significantly increases the risk of ILD. These results provide risk prediction for ILD related to ALK TKIs and support pharmacovigilance to promote safe prescribing in oncology.

The results of the in vitro stability experiment showed that the selected mixed micelle (F6) was stable at both room temperature and 4 °C, with only minor changes in size and PDI. Our results indicate great potential for the developed Soluplus-TPGS mixed micelles as a delivery system for BGT.

P4, N=14, Pfizer, Inc

Subsequent in vitro bioassay of the top 40 hits identified two compounds with low micromolar IC50 values. Remarkably, one of the identified leads possesses a novel chemotype compared to known ALK inhibitors.

P1, N=56, Completed, Haihe Biopharma Co., Ltd. | Unknown status --> Completed | N=113 --> 56

ORNi-PCR followed by ddPCR/real-time PCR enables highly sensitive and accurate detection of ALK mutations by liquid biopsy. Although the clinical data are limited, our results show that these methods are potentially useful for identifying ALK-TKI-resistant NSCLC at the early recurrent phase.

Similarly, more frequent surveillance imaging than what is considered standard-of-care may identify disease progression earlier than what is expected in real-world clinical practice and therefore embellish the magnitude of benefit between a targeted therapy and the control arm. While targeted therapies have provided clinical benefit for individuals with oncogenic driven NSCLC, physicians and patients must be cognizant that clinical trial deviations from standard-of-care imaging practices may have embellished the magnitude of benefit for several of these therapies.

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

In PD-L1 TPS ≥50% EGFR/ALK wild-type patients, only patients who have never smoked benefited from first-line Chemo-IO over IO-alone, suggesting IO-alone may be preferable for patients with smoking history to spare chemotherapy toxicity. Tobacco-related mutational signature may potentially reduce stigma, improve patient stratification, and guide more precise IO-based treatment in patients with NSCLC.