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SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition - npj Precision Oncology

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SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition - npj Precision Oncology

Despite the promising antitumor activity of SHP2 inhibitors in RAS-dependent tumours, overall responses have been limited by their narrow therapeutic window. Like with all MAPK pathway inhibitors, this is likely the result of compensatory pathway activation mechanisms. However, the underlying mechanisms of resistance to SHP2 inhibition remain unknown. The E3 ligase SMURF2 limits TGFβ activity by ubiquitinating and targeting the TGFβ receptor for proteosome degradation.

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SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition - npj Precision Oncology

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SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition - npj Precision Oncology

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