Yale Cancer Center Precision Medicine Tumor Board: one tumour, multiple targets

• Published in: The lancet oncology Vol. 19; no. 12; pp. 1567 - 1568
• Main Authors: Stewart, Tyler, Finberg, Karin, Walther, Zenta, Sklar, Jeffrey L, Hafez, Navid, Eder, Joseph P, Anderson, Karen, Wilson, Frederick, Goldberg, Sarah B
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01.12.2018; Elsevier Limited
• Subjects: Antigens; Cancer therapies; Cell cycle; Cell surface; Chemotherapy; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; Enzyme inhibitors; Fibroblast growth factor receptor 2; Fibroblast growth factor receptors; Fibroblasts; Genes; Growth factors; Kinases; Liver; Lung cancer; MEK inhibitors; Melanoma; Metastases; Metastasis; Mutation; p53 Protein; Patients; Precision medicine; Protein-tyrosine kinase; Proteins; Sarcoma; Signal transduction; Splicing; Thyroid cancer; Tumors; United States > US
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(18)30759-9

FGFR2 encodes fibroblast growth factor receptor 2, a tyrosine kinase that acts as a cell-surface receptor for fibroblast growth factors. Trametinib is a reversible MEK1/2 inhibitor approved in the USA, both in combination with dabrafenib (a BRAF kinase inhibitor) for patients with melanoma, non-small-cell lung cancer, and anaplastic thyroid cancer containing specific BRAF mutations (V600E, V600K), and as monotherapy for BRAF-mutant metastatic melanoma. Clinical follow-up The patient consented to off-label use of the MEK inhibitor trametinib, which was administered orally at the standard dose of 2 mg daily. 18 days after starting trametinib, he became septic with disseminated bacterial and fungal infections that required hospital admission. For more on aberrant CDKN2A splicing see Oncogene 2003; 22: 4444–48 For more on malignant progression and p53 see Cancer Cell 2014; 25: 304–17 For more on Sorting Intolerant From Tolerant see Nucleic Acids Res 2012; 40: 452–57 For more on Polyphen-2 see Nat Methods 2010; 7: 248–49 For more on FGFR signalling see Clin Cancer Res 2015; 21: 2684–94 For more on FGFR2 mutations see Oncogene 1997; 15: 817–26 For more on histiocytic sarcoma see N Engl J Med 2018; 378: 1945–47 For the abstract reporting palbociclib treatment see Proc Am Soc Clin Oncol 2018; 36 (abstr 2532) For more on targeting alterations in FGFR2 see J Clin Oncol 2018; 36: 276–82 TS and KF contributed equally SBG reports personal fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Genentech, Spectrum and Amgen, and grants from AstraZeneca, outside the submitted work.