ALK (Anaplastic lymphoma kinase)

P1/2, N=296, Active, not recruiting, Inhibrx Biosciences, Inc | Recruiting --> Active, not recruiting

P1/2, N=36, Terminated, SignalChem Lifesciences Corporation | N=92 --> 36 | Trial completion date: Sep 2028 --> Dec 2025 | Recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Dec 2025; Lack of efficacy and enrollment challenges

P3, N=339, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026

P3, N=1200, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC.

We outline mechanisms of action, clinical efficacy, and limitations of FDA-approved tyrosine kinase inhibitors (TKIs) and emerging agents, with emphasis on resistance pathways, both on-target and bypass-mediated, observed during treatment with drugs such as osimertinib, crizotinib, sotorasib, and entrectinib. The role of next-generation sequencing (NGS), liquid biopsy, and comprehensive biomarker profiling in guiding personalized therapy selection is also discussed, along with strategies for sequential therapy and rational combination approaches.

ALCL is an uncommon neoplasm in the pediatric population and rarely presents as a primary lung tumor. However, when unusual pulmonary lesions are encountered, especially in children, ALCL should be part of the differential diagnosis.

Despite the higher grade ≥3 AE incidence, similar rates of dose reduction, interruption, or discontinuation suggest these AEs are manageable. Lorlatinib remains a first-line treatment option for ALK+ metastatic non-small cell lung cancer, offering meaningful benefits to appropriate patients.

Careful assessment of nuclear morphology and cell distribution patterns can provide valuable diagnostic clues to prevent misdiagnosis. This rare cytological presentation offers critical educational insights for cytopathologists and underscores the diagnostic value of FNA cytology, particularly when integrated with immunophenotypic analysis and retrospective morphological review in evaluating morphologically challenging lymphoid malignancies.

RDD of the lung and mediastinum is rare, with a wide range of ages. Histologically, there are often lymphoid follicles with germinal centers and interstitial fibrosis or sclerosis. This together with the expression of BCL2 and CD30 in the histiocytes can lead to misdiagnosis of lymphomas or other lymphoproliferative diseases or missed diagnosis, particularly in the mediastinum. Careful histological examination for the diagnostic feature of emperipolesis together with characteristic Cyclin D1, OCT2, S100 protein, and CD68 positivity are important clues for accurate diagnosis.

Since the first BsAb approval in 2014, the field has rapidly expanded, with solid tumor oncology advancing dynamically. The major focus has been on combining BsAbs with immunotherapy strategies, followed by targeting known oncogenic pathways. The shift toward biotechnology-led innovation underscores the growing therapeutic and financial interest in this field. Optimizing the efficacy and safety of these molecules is key to paving the way for the next era of immune and precision oncology.

This effort culminated in the identification of compound 8q, which demonstrated potent and selective anti-tumor efficacy against ALK (anaplastic lymphoma kinase) -positive cancer cells (NCI-H2228 and Karpas-299), significantly outperforming ceritinib in enzymatic and cellular assays...The RMSD and RMSF analyses confirmed enhanced conformational stability of the 8q-ALK complex compared to the apo protein. Collectively, these findings highlight 8q as a promising lead compound for the development of novel ALK inhibitors with a favorable efficacy and safety profile.