Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Changing ALK-TKI-Resistance Mechanisms in Rebiopsies of ALK-Rearranged NSCLC: ALK- and BRAF-Mutations Followed by Epithelial-Mesenchymal Transition

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Genetic Biomarkers in Melanoma of the Ocular Region: What the Medical Oncologist Should Know

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  3. Disorders of Sex Development-Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  4. Neonatal HDL counteracts placental vascular inflammation via S1P-S1PR1 axis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Fluorescent Analogues of Human α-Calcitonin Gene-Related Peptide with Potent Vasodilator Activity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. The molecular profile of mucosal melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Behandling af tymom og thymuskarcinom

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Molecular Characterization of the Danish Prion Diseases Cohort With Special Emphasis on Rare and Unique Cases

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Anaplastic lymphoma-kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is prone to developing heterogeneous, only partly known mechanisms of resistance to ALK-tyrosine-kinase-inhibitors (ALK-TKIs). We present a case of a 38-year old male, who never smoked with disseminated ALK-rearranged (EML4 (20) - ALK (20) fusion variant 2) lung adenocarcinoma, who received four sequentially different ALK-TKIs and two lines of chemotherapy in-between. We observed significant clinical benefit by the first three ALK-TKIs (Crizotinib, Ceritinib, Alectinib) and chemotherapy with Pemetrexed, resulting in overall survival over 3 years. Longitudinal assessment of progressions by rebiopsies from hepatic metastases showed different mechanisms of resistance to each ALK-TKI, including secondary ALK-mutations and the downstream p.V600E BRAF-mutation that had not been linked to second-generation ALK-TKIs before. Ultimately, in connection with terminal rapid progression and resistance to Alectinib and Lorlatinib, we identified phenotypical epithelial-mesenchymal transition (EMT) of newly occurred metastatic cells, a phenomenon not previously related to these two ALK-TKIs. This resistance heterogeneity suggests a continuously changing disease state. Sequential use of different generation's ALK-TKIs and combination therapies may yield prolonged responses with satisfactory quality of life in patients with advanced ALK-positive NSCLC. However, the development of EMT is a major hurdle and may explain rapid disease progression and lack of response to continued ALK-inhibition.

OriginalsprogEngelsk
TidsskriftInternational Journal of Molecular Sciences
Vol/bind21
Udgave nummer8
ISSN1661-6596
DOI
StatusUdgivet - 19 apr. 2020

ID: 59998373