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  Do inhibitors targeted against mutant oncogenic kinases act via kinase degradation-induced immune activation?

Söding, J. (2021). Do inhibitors targeted against mutant oncogenic kinases act via kinase degradation-induced immune activation?. Unpublished Manuscript.

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3345235.pdf (Preprint), 614KB
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3345235.pdf
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Revised version of: http://hdl.handle.net/21.11116/0000-0008-9049-3
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 Creators:
Söding, J.1, Author              
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1Research Group of Computational Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1933286              

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 Abstract: Targeted cancer therapies by small-molecule inhibitors of receptor tyrosine and other kinases have achieved great success in recent years. Most targeted medications specifically inhibit a protein kinase mutated in the patient's tumor. Although many possible mechanisms have been investigated, the drugs' astounding efficacies are not well understood. We propose a unifying mechanism of action. Strong binding by the inhibitor could lead to increased ubiquitination and degradation by the proteasome, boosting the presentation of kinase-associated neoantigen peptides. This would facilitate tumor cell recognition by T cells, leading to a sustained immune attack. The model suggests that the as yet inevitable failure to shrink tumors further after a few months might be caused by a transition to chronic inflammation. If true, the model has a multitude of implications for cancer and clinical research.

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Language(s): eng - English
 Dates: 2021-09-21
 Publication Status: Not specified
 Pages: -
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 Table of Contents: -
 Rev. Type: No review
 Identifiers: DOI: 10.17617/2.3345235
 Degree: -

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