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Fig. 3 | Journal of Biomedical Science

Fig. 3

From: Biomarkers beyond BRCA: promising combinatorial treatment strategies in overcoming resistance to PARP inhibitors

Fig. 3

Overcoming resistance to PARPi by Marker-guided effective therapy (Mget) strategies. a RTK-mediated PARPi resistance. (1) c-MET phosphorylates PARP1 at Y907 to upregulate PARylation and prevent the binding of PARPi, thereby resulting in PARPi resistance. (2) Heterodimerization of EGFR and c-MET contributes to PARPi resistance through phosphorylation of PARP1-Y907. (3) Phosphorylated ALK (p-ALK) promotes HR activity and PARPi resistance by directly phosphorylating CDK9 at Y19. p-Y19 CDK9 facilitates nuclear localization of CDK9 and interacts with cyclin T to form a p-TEFb (CDK9/cyclin T) complex, which turns on transcription of HR repair genes. b Marker-guided effective therapy (Mget) strategies to overcome resistance to PARPi. Expression of RTKs and their specific phosphorylated substrates detected in patient tumor tissues could be utilized to predict PARPi resistance and select the right patients for treatment with PARPi in combination with the specific RTK inhibitors

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Journal of Biomedical Science

ISSN: 1423-0127