Please use this identifier to cite or link to this item:
doi:10.22028/D291-39403
Title: | An In Vitro Analysis of TKI-Based Sequence Therapy in Renal Cell Carcinoma Cell Lines |
Author(s): | Zaccagnino, Angela Vynnytska-Myronovska, Bozhena Stöckle, Michael Junker, Kerstin |
Language: | English |
Title: | International Journal of Molecular Sciences |
Volume: | 24 |
Issue: | 6 |
Publisher/Platform: | MDPI |
Year of Publication: | 2023 |
Free key words: | renal cell carcinoma sunitinib resistance tyrosine kinase inhibitor sequential treatment receptor tyrosine kinases drug resistance cell signaling |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
Abstract: | The tyrosine kinase inhibitor (TKI) cabozantinib might impede the growth of the sunitinibresistant cell lines by targeting MET and AXL overexpression in metastatic renal cell carcinoma (mRCC). We studied the role of MET and AXL in the response to cabozantinib, particularly following long-term administration with sunitinib. Two sunitinib-resistant cell lines, 786-O/S and Caki-2/S, and the matching 786-O/WT and Caki-2/WT cells were exposed to cabozantinib. The drug response was cell-line-specific. The 786-O/S cells were less growth-inhibited by cabozantinib than 786-O/WT cells (p-value = 0.02). In 786-O/S cells, the high level of phosphorylation of MET and AXL was not affected by cabozantinib. Despite cabozantinib hampering the high constitutive phosphorylation of MET, the Caki-2 cells showed low sensitivity to cabozantinib, and this was independent of sunitinib pretreatment. In both sunitinib-resistant cell lines, cabozantinib increased Src-FAK activation and impeded mTOR expression. The modulation of ERK and AKT was cell-line-specific, mirroring the heterogeneity among the patients. Overall, the MET- and AXL-driven status did not affect cell responsiveness to cabozantinib in the second-line treatment. The activation of Src-FAK might counteract cabozantinib activity and contribute to tumor survival and may be considered an early indicator of therapy response. |
DOI of the first publication: | 10.3390/ijms24065648 |
URL of the first publication: | https://www.mdpi.com/1422-0067/24/6/5648 |
Link to this record: | urn:nbn:de:bsz:291--ds-394036 hdl:20.500.11880/35527 http://dx.doi.org/10.22028/D291-39403 |
ISSN: | 1422-0067 |
Date of registration: | 29-Mar-2023 |
Description of the related object: | Supplementary Materials |
Related object: | https://www.mdpi.com/article/10.3390/ijms24065648/s1 |
Faculty: | M - Medizinische Fakultät |
Department: | M - Urologie und Kinderurologie |
Professorship: | M - Prof. Dr. Michael Stöckle |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
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ijms-24-05648-v2.pdf | 3,58 MB | Adobe PDF | View/Open |
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