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Intrahepatic cholangiocarcinoma (ICC) is the second most prevalent liver cancer after hepatocellular carcinoma and is characterized by high malignancy and poor prognosis. Gemcitabine combined with cisplatin is the standard first-line therapy for metastatic or unresectable ICC. The combination of immunotherapy and targeted therapy represents a promising new direction for ICC treatment. Common genetic mutations in ICC include those in TP53, FGFR2, IDH1/2, and KRAS. MET alterations such as fusions and amplifications are rare in ICC. However, limited research has been conducted on the efficacy of specific MET inhibitors. We present two cases: the first with refractory ICC treated with a combination of immunotherapy and targeted therapy, harboring a ZKSCAN1-MET fusion and the second with a metastatic ICC with MET amplification. Both patients demonstrated a significant clinical response to crizotinib, a MET-specific tyrosine kinase inhibitor.
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http://dx.doi.org/10.1007/s12672-025-02930-4 | DOI Listing |
Bioorg Chem
September 2025
Department of Pharmacy, Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:
RET tyrosine kinase, a key regulator of cellular signaling, is abnormally activated due to mutations or fusions in various cancers, making it an important therapeutic target. Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
August 2025
Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, PR China. Electronic address:
Crizotinib, alectinib, and lorlatinib are tyrosine kinase inhibitors used sequentially in non-small cell lung cancer (NSCLC) therapy. Therapeutic drug monitoring (TDM) is valuable during sequential treatment, enabling simultaneous quantification. Consequently, an analytical method capable of multiplexing these three compounds into a single assay is highly applicable for routine TDM.
View Article and Find Full Text PDFAm J Hematol
September 2025
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma with poor outcomes using standard chemotherapy. In this multi-institutional retrospective study, we analyzed 39 cases of ALK+ LBCL identified at six US academic centers from 2002 to 2024, with treatment including conventional cytotoxic regimens in frontline and biologically informed and nonchemotherapy-based strategies in the relapsed setting. Ninety-two percent of patients received frontline anthracycline-based chemotherapy; 43% received intensified regimens, and 15% underwent upfront autologous stem cell transplantation (ASCT).
View Article and Find Full Text PDFMol Oncol
August 2025
Department of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, The Netherlands.
Clinical outcomes in ROS1-fusion positive (ROS1+) non-small cell lung cancer (NSCLC) by fusion partner and resistance mechanisms are limited. This cohort study included 56 ROS1+ patients (FISH or NGS confirmed); fusion partners were identified in 27 cases, including CD74 (n = 10), EZR (n = 7), and SDC4 (n = 7). Clinical data were available for 50 patients (median age 62; 51% female; 32% never-smokers).
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Gastric cancer remains one of the most prevalent gastrointestinal malignancies, with certain subtypes, such as poorly cohesive carcinoma-including signet ring cell carcinoma (SRCC)-exhibiting aggressive progression and poor prognosis. Mesenchymal epithelial transition (MET) amplification, a relatively rare oncogenic driver in gastric cancer (~2-10.2% of cases), has been associated with resistance to conventional therapies and dismal survival (median <6 months in metastatic cases).
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