: Characteristic of some rare pediatric and adult malignancies, addiction to the oncogene family is also observed in a small fraction of common cancers. Inhibition of their protein products, the Trk kinases, proved a successful treatment strategy for these tumors.: The current paper reviews the clinical development of larotrectinib, a selective inhibitor of the Trk kinase family, for the treatment of fusion-positive cancers. The manuscript includes an overview of the efficacy, safety, pharmacokinetics and pharmacodynamics. The authors sum up by providing the reader with their expert opinion on larotrectinib and its potential future use.: Larotrectinib showed tolerability and high efficacy, regardless of the primary site. In 2018, larotrectinib was granted by the Food and Drug Administration a tissue-agnostic approval for the treatment of solid tumors harboring an fusion. The major challenges will be the implementation of the screening for fusions in the general oncologic population, and the incorporation of larotrectinib into the therapeutic algorithms.
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http://dx.doi.org/10.1080/14656566.2021.1876664 | DOI Listing |
JAMA
January 2025
CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, University of Florence, AOU Careggi, Florence, Italy.
Importance: Essential thrombocythemia, a clonal myeloproliferative neoplasm with excessive platelet production, is associated with an increased risk of thrombosis and bleeding. The annual incidence rate of essential thrombocythemia in the US is 1.5/100 000 persons.
View Article and Find Full Text PDFInvest New Drugs
January 2025
School of Life Sciences, Jilin University, Changchun, China.
Due to the emergence of drug resistance, androgen receptor (AR)-targeted drugs still pose great challenges in the treatment of prostate cancer, and it is urgent to explore an innovative therapeutic strategy. MK-1775, a highly selective WEE1 inhibitor, is shown to have favorable therapeutic benefits in several solid tumor models. Recent evidence suggests that the combination of MK-1775 with DNA-damaging agents could lead to enhanced antitumor efficacy.
View Article and Find Full Text PDFInt J Gynecol Pathol
January 2025
Department of Pathology and Immunology, Washington University.
High-grade serous carcinomas (HGSCs) with homologous recombination deficiency (HRD) respond favorably to platinum therapy and poly ADP ribose polymerase (PARP) inhibitors. Mutations in BRCA1 and BRCA2 commonly cause HRD and have been associated with Solid, pseudoEndometrioid, and Transitional-like (SET-like) histology. Mutations in other homologous recombination repair (HRR) genes as well as epigenetic changes can also result in HRD; however, morphologic correlates have not been well-explored in these cases.
View Article and Find Full Text PDFThyroid
January 2025
Faculty of Medicine and Health, Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, Australia.
Tumor-infiltrating lymphocytes (TILs) are a protective prognostic factor in several solid tumors and predict response to immune checkpoint inhibitor therapy. The prognostic impact of TILs in medullary thyroid cancer (MTC) is poorly understood. In this retrospective cohort study, we assessed the TILs profile of primary MTC tumors using the International TILs Working Group system and correlated this with clinicopathological prognostic variables, including the International Medullary Thyroid Cancer Grading System (IMTCGS) grade and survival outcomes.
View Article and Find Full Text PDFJ Magn Reson Imaging
January 2025
Department of Radiology, Peking University Third Hospital, Beijing, China.
Background: The spinal column is a frequent site for metastases, affecting over 30% of solid tumor patients. Identifying the primary tumor is essential for guiding clinical decisions but often requires resource-intensive diagnostics.
Purpose: To develop and validate artificial intelligence (AI) models using noncontrast MRI to identify primary sites of spinal metastases, aiming to enhance diagnostic efficiency.
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