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. 2022 Oct 25;29:86. doi: 10.1186/s12929-022-00870-7

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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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