PROTAC-mediated CDK degradation differentially impacts cancer cell cycles due to heterogeneity in kinase dependencies

Background Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological a...

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Published in:	British journal of cancer Vol. 129; no. 8; pp. 1238 - 1250
Main Authors:	Kumarasamy, Vishnu, Gao, Zhe, Zhao, Bosheng, Jiang, Baishan, Rubin, Seth M., Burgess, Kevin, Witkiewicz, Agnieszka K., Knudsen, Erik S.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 12.10.2023 Nature Publishing Group
Subjects:	631/337/505 631/92/436/434 Animals Biomedical and Life Sciences Biomedicine Cancer Research Cell activation Cell cycle Cell Cycle - drug effects Cell Line, Tumor Cell proliferation Cell Proliferation - drug effects Chimeras Cyclin E Cyclin-dependent kinase 2 Cyclin-dependent kinase 4 Cyclin-Dependent Kinase 4 - antagonists & inhibitors Cyclin-Dependent Kinase 4 - metabolism Cyclin-Dependent Kinase 6 - antagonists & inhibitors Cyclin-Dependent Kinase 6 - metabolism Cyclin-dependent kinases Drug Resistance Epidemiology Humans INK4a protein Kinases Mice Molecular Medicine Oncology Organoids p16 Protein Piperazines - pharmacology Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Proteolysis Proteolysis - drug effects Pyridines - chemistry Pyridines - pharmacology Thalidomide - analogs & derivatives Thalidomide - pharmacology Tumors Xenograft Model Antitumor Assays
ISSN:	0007-0920, 1532-1827, 1532-1827
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Abstract	Background Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological agents that target these kinases. Methods We utilized proteolysis-targeted chimeras (PROTACs) that are conjugated with palbociclib (Palbo-PROTAC) to degrade both CDK4 and CDK6. FN-POM was synthesized by chemically conjugating pomalidomide moiety with a multi-kinase inhibitor, FN-1501. Patient derived PDAC organoids and PDX model were utilized to investigate the effect of FN-POM in combination with palbociclib. Results Palbo-PROTAC mediates differential impact on cell cycle in different tumor models, indicating that the dependencies to CDK4 and 6 kinases are heterogenous. Cyclin E overexpression uncouples cell cycle from CDK4/6 and drives resistance to palbo-PROTAC. Elevated expression of P16INK4A antagonizes PROTAC-mediated degradation of CDK4 and 6. FN-POM degrades cyclin E and CDK2 and inhibits cell cycle progression in P16INK4A-high tumor models. Combination of palbociclib and FN-POM cooperatively inhibit tumor cell proliferation via RB activation. Conclusion Resistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach.
AbstractList	Background Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological agents that target these kinases. Methods We utilized proteolysis-targeted chimeras (PROTACs) that are conjugated with palbociclib (Palbo-PROTAC) to degrade both CDK4 and CDK6. FN-POM was synthesized by chemically conjugating pomalidomide moiety with a multi-kinase inhibitor, FN-1501. Patient derived PDAC organoids and PDX model were utilized to investigate the effect of FN-POM in combination with palbociclib. Results Palbo-PROTAC mediates differential impact on cell cycle in different tumor models, indicating that the dependencies to CDK4 and 6 kinases are heterogenous. Cyclin E overexpression uncouples cell cycle from CDK4/6 and drives resistance to palbo-PROTAC. Elevated expression of P16INK4A antagonizes PROTAC-mediated degradation of CDK4 and 6. FN-POM degrades cyclin E and CDK2 and inhibits cell cycle progression in P16INK4A-high tumor models. Combination of palbociclib and FN-POM cooperatively inhibit tumor cell proliferation via RB activation. Conclusion Resistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological agents that target these kinases. We utilized proteolysis-targeted chimeras (PROTACs) that are conjugated with palbociclib (Palbo-PROTAC) to degrade both CDK4 and CDK6. FN-POM was synthesized by chemically conjugating pomalidomide moiety with a multi-kinase inhibitor, FN-1501. Patient derived PDAC organoids and PDX model were utilized to investigate the effect of FN-POM in combination with palbociclib. Palbo-PROTAC mediates differential impact on cell cycle in different tumor models, indicating that the dependencies to CDK4 and 6 kinases are heterogenous. Cyclin E overexpression uncouples cell cycle from CDK4/6 and drives resistance to palbo-PROTAC. Elevated expression of P16INK4A antagonizes PROTAC-mediated degradation of CDK4 and 6. FN-POM degrades cyclin E and CDK2 and inhibits cell cycle progression in P16INK4A-high tumor models. Combination of palbociclib and FN-POM cooperatively inhibit tumor cell proliferation via RB activation. Resistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach. BackgroundCyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological agents that target these kinases.MethodsWe utilized proteolysis-targeted chimeras (PROTACs) that are conjugated with palbociclib (Palbo-PROTAC) to degrade both CDK4 and CDK6. FN-POM was synthesized by chemically conjugating pomalidomide moiety with a multi-kinase inhibitor, FN-1501. Patient derived PDAC organoids and PDX model were utilized to investigate the effect of FN-POM in combination with palbociclib.ResultsPalbo-PROTAC mediates differential impact on cell cycle in different tumor models, indicating that the dependencies to CDK4 and 6 kinases are heterogenous. Cyclin E overexpression uncouples cell cycle from CDK4/6 and drives resistance to palbo-PROTAC. Elevated expression of P16INK4A antagonizes PROTAC-mediated degradation of CDK4 and 6. FN-POM degrades cyclin E and CDK2 and inhibits cell cycle progression in P16INK4A-high tumor models. Combination of palbociclib and FN-POM cooperatively inhibit tumor cell proliferation via RB activation.ConclusionResistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological agents that target these kinases.BACKGROUNDCyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological agents that target these kinases.We utilized proteolysis-targeted chimeras (PROTACs) that are conjugated with palbociclib (Palbo-PROTAC) to degrade both CDK4 and CDK6. FN-POM was synthesized by chemically conjugating pomalidomide moiety with a multi-kinase inhibitor, FN-1501. Patient derived PDAC organoids and PDX model were utilized to investigate the effect of FN-POM in combination with palbociclib.METHODSWe utilized proteolysis-targeted chimeras (PROTACs) that are conjugated with palbociclib (Palbo-PROTAC) to degrade both CDK4 and CDK6. FN-POM was synthesized by chemically conjugating pomalidomide moiety with a multi-kinase inhibitor, FN-1501. Patient derived PDAC organoids and PDX model were utilized to investigate the effect of FN-POM in combination with palbociclib.Palbo-PROTAC mediates differential impact on cell cycle in different tumor models, indicating that the dependencies to CDK4 and 6 kinases are heterogenous. Cyclin E overexpression uncouples cell cycle from CDK4/6 and drives resistance to palbo-PROTAC. Elevated expression of P16INK4A antagonizes PROTAC-mediated degradation of CDK4 and 6. FN-POM degrades cyclin E and CDK2 and inhibits cell cycle progression in P16INK4A-high tumor models. Combination of palbociclib and FN-POM cooperatively inhibit tumor cell proliferation via RB activation.RESULTSPalbo-PROTAC mediates differential impact on cell cycle in different tumor models, indicating that the dependencies to CDK4 and 6 kinases are heterogenous. Cyclin E overexpression uncouples cell cycle from CDK4/6 and drives resistance to palbo-PROTAC. Elevated expression of P16INK4A antagonizes PROTAC-mediated degradation of CDK4 and 6. FN-POM degrades cyclin E and CDK2 and inhibits cell cycle progression in P16INK4A-high tumor models. Combination of palbociclib and FN-POM cooperatively inhibit tumor cell proliferation via RB activation.Resistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach.CONCLUSIONResistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach.
Author	Rubin, Seth M. Zhao, Bosheng Witkiewicz, Agnieszka K. Knudsen, Erik S. Kumarasamy, Vishnu Gao, Zhe Burgess, Kevin Jiang, Baishan
Author_xml	– sequence: 1 givenname: Vishnu surname: Kumarasamy fullname: Kumarasamy, Vishnu organization: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute – sequence: 2 givenname: Zhe surname: Gao fullname: Gao, Zhe organization: Department of Chemistry, Texas A&M University – sequence: 3 givenname: Bosheng surname: Zhao fullname: Zhao, Bosheng organization: Department of Chemistry, Texas A&M University – sequence: 4 givenname: Baishan orcidid: 0000-0001-6796-9500 surname: Jiang fullname: Jiang, Baishan organization: Department of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University – sequence: 5 givenname: Seth M. surname: Rubin fullname: Rubin, Seth M. organization: Department of Chemistry and Biochemistry, University of California – sequence: 6 givenname: Kevin surname: Burgess fullname: Burgess, Kevin organization: Department of Chemistry, Texas A&M University – sequence: 7 givenname: Agnieszka K. surname: Witkiewicz fullname: Witkiewicz, Agnieszka K. organization: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute – sequence: 8 givenname: Erik S. orcidid: 0000-0002-5130-5969 surname: Knudsen fullname: Knudsen, Erik S. email: Erik.Knudsen@roswellpark.org organization: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute
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Cites_doi	10.1038/s43018-021-00174-z 10.1101/gad.13.12.1501 10.1021/acs.jmedchem.7b01261 10.1038/s41523-018-0092-4 10.1158/2159-8290.CD-20-1726 10.1038/nature07884 10.1016/j.ejmech.2021.113849 10.1038/s41586-019-1056-z 10.3389/fphar.2020.580251 10.1182/blood-2014-02-558114 10.1126/science.aat0572 10.1038/s41586-021-03445-y 10.1158/0008-5472.CAN-20-2275 10.1136/gutjnl-2020-321000 10.1126/scisignal.2004088 10.1186/s40364-020-0182-y 10.1038/onc.2016.379 10.1016/0092-8674(93)90636-5 10.1038/s41467-021-23612-z 10.1038/s41586-021-03474-7 10.1021/jm049354h 10.1126/science.aaw2106 10.1039/C9CC00163H 10.1016/j.ccell.2021.08.009 10.3389/fonc.2021.693104 10.1038/s41388-022-02362-2 10.1016/j.celrep.2022.110448 10.1038/s41392-019-0101-6 10.1016/j.ctrv.2016.03.002 10.1002/anie.201901336 10.1038/nrd.2016.211 10.1080/17460441.2019.1659242 10.1126/sciadv.abb2210 10.1186/s13058-022-01510-6 10.1200/PO.21.00002 10.1016/j.ccell.2020.03.010 10.1002/anie.202004087 10.1038/s41388-018-0650-0 10.1038/s41580-021-00404-3 10.1158/0008-5472.CAN-21-2428 10.1038/nature18611 10.1016/j.ccell.2018.11.006 10.1038/s41416-022-01990-5 10.1128/MCB.15.8.4215 10.1080/15384101.2018.1502567
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References	Pack, Daigh, Chung, Meyer (CR18) 2021; 12 Sievers, Petzold, Bunker, Renneville, Slabicki, Liddicoat (CR29) 2018; 362 Zhao, Burgess (CR25) 2019; 55 Kumarasamy, Nambiar, Wang, Rosenheck, Witkiewicz, Knudsen (CR10) 2022; 41 Knudsen, Kumarasamy, Chung, Ruiz, Vail, Tzetzo (CR36) 2021; 70 Thu, Soria-Bretones, Mak, Cescon (CR5) 2018; 17 Knudsen, Kumarasamy, Nambiar, Pearson, Vail, Rosenheck (CR22) 2022; 38 Kumarasamy, Vail, Nambiar, Witkiewicz, Knudsen (CR15) 2021; 81 Watt, Goel (CR8) 2022; 24 Knudsen, Kumarasamy, Ruiz, Sivinski, Chung, Grant (CR14) 2019; 38 Konstantinidou, Li, Zhang, Wang, Shaabani, Ter Brake (CR39) 2019; 14 Li, Razavi, Li, Toy, Liu, Ping (CR31) 2018; 34 Guarducci, Bonechi, Benelli, Biagioni, Boccalini, Romagnoli (CR32) 2018; 4 Teng, Jiang, He, Kwiatkowski, Donovan, Mills (CR44) 2020; 59 Yang, Li, Bhatt, Dickler, Giri, Scaltriti (CR33) 2017; 36 DeGregori, Kowalik, Nevins (CR4) 1995; 15 Sherr, Roberts (CR3) 1999; 13 Hati, Zallocchi, Hazlitt, Li, Vijayakumar, Min (CR45) 2021; 226 Sun, Gao, Yang, He, Wu, Song (CR40) 2019; 4 Asghar, Kanani, Roylance, Mittnacht (CR12) 2022; 6 Sherr (CR2) 1993; 73 Lai, Crews (CR23) 2017; 16 Hamilton, Infante (CR13) 2016; 45 Gao, Wang, Song (CR28) 2020; 8 Li, Zou, Zhang, Zhang, Xu, Li (CR34) 2020; 11 Toogood, Harvey, Repine, Sheehan, VanderWel, Zhou (CR38) 2005; 48 Placke, Faber, Nonami, Putwain, Salih, Heidel (CR19) 2014; 124 Matthews, Bertoli, de Bruin (CR1) 2022; 23 Matyskiela, Lu, Ito, Pagarigan, Lu, Miller (CR27) 2016; 535 Li, Jiang, Guo, Shao, Del Priore, Chang (CR16) 2022; 12 Chaikovsky, Li, Jeng, Loebell, Lee, Murray (CR7) 2021; 592 Wu, Yang, Xiong, Li, Ito, Ahmed (CR21) 2021; 2 Schaefer, Hemming, Lundberg, Serrata, Goldaracena, Liu (CR43) 2022; 127 Guiley, Stevenson, Lou, Barkovich, Kumarasamy, Wijeratne (CR17) 2019; 366 Gao, Aksoy, Dogrusoz, Dresdner, Gross, Sumer (CR9) 2013; 6 Alvarez-Fernandez, Malumbres (CR20) 2020; 37 Simoneschi, Rona, Zhou, Jeong, Jiang, Milletti (CR6) 2021; 592 Bertucci, Ng, Patsouris, Droin, Piscuoglio, Carbuccia (CR11) 2019; 569 Zhang, Golomb, Meyerson (CR35) 2022; 82 George, Qureshi, Omene, Toppmeyer, Ganesan (CR37) 2021; 11 Freeman-Cook, Hoffman, Miller, Almaden, Chionis, Zhang (CR42) 2021; 39 Jiang, Wang, Donovan, Liang, Fischer, Zhang (CR24) 2019; 58 Soucy, Smith, Milhollen, Berger, Gavin, Adhikari (CR30) 2009; 458 Wang, Zhi, Jin, Lu, Lin, Yuan (CR26) 2018; 61 Fassl, Brain, Abu-Remaileh, Stukan, Butter, Stepien (CR41) 2020; 6 CJ Sherr (2399_CR2) 1993; 73 KL Thu (2399_CR5) 2018; 17 M Alvarez-Fernandez (2399_CR20) 2020; 37 ME Matyskiela (2399_CR27) 2016; 535 Z Li (2399_CR34) 2020; 11 US Asghar (2399_CR12) 2022; 6 J Gao (2399_CR9) 2013; 6 KZ Guiley (2399_CR17) 2019; 366 A Fassl (2399_CR41) 2020; 6 X Sun (2399_CR40) 2019; 4 D Simoneschi (2399_CR6) 2021; 592 Z Zhang (2399_CR35) 2022; 82 QL Sievers (2399_CR29) 2018; 362 ES Knudsen (2399_CR14) 2019; 38 C Guarducci (2399_CR32) 2018; 4 Y Wang (2399_CR26) 2018; 61 M Teng (2399_CR44) 2020; 59 E Hamilton (2399_CR13) 2016; 45 V Kumarasamy (2399_CR15) 2021; 81 X Wu (2399_CR21) 2021; 2 B Jiang (2399_CR24) 2019; 58 M Konstantinidou (2399_CR39) 2019; 14 AC Chaikovsky (2399_CR7) 2021; 592 ES Knudsen (2399_CR22) 2022; 38 B Zhao (2399_CR25) 2019; 55 C Yang (2399_CR33) 2017; 36 V Kumarasamy (2399_CR10) 2022; 41 F Bertucci (2399_CR11) 2019; 569 J DeGregori (2399_CR4) 1995; 15 Z Li (2399_CR31) 2018; 34 ES Knudsen (2399_CR36) 2021; 70 S Hati (2399_CR45) 2021; 226 IM Schaefer (2399_CR43) 2022; 127 HK Matthews (2399_CR1) 2022; 23 T Placke (2399_CR19) 2014; 124 S Gao (2399_CR28) 2020; 8 MA George (2399_CR37) 2021; 11 CJ Sherr (2399_CR3) 1999; 13 K Freeman-Cook (2399_CR42) 2021; 39 Q Li (2399_CR16) 2022; 12 AC Lai (2399_CR23) 2017; 16 TA Soucy (2399_CR30) 2009; 458 AC Watt (2399_CR8) 2022; 24 PL Toogood (2399_CR38) 2005; 48 LR Pack (2399_CR18) 2021; 12
References_xml	– volume: 2 start-page: 429 year: 2021 end-page: 43 ident: CR21 article-title: Distinct CDK6 complexes determine tumor cell response to CDK4/6 inhibitors and degraders publication-title: Nat Cancer doi: 10.1038/s43018-021-00174-z – volume: 13 start-page: 1501 year: 1999 end-page: 12 ident: CR3 article-title: CDK inhibitors: positive and negative regulators of G1-phase progression publication-title: Genes Dev doi: 10.1101/gad.13.12.1501 – volume: 61 start-page: 1499 year: 2018 end-page: 518 ident: CR26 article-title: Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)p henyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia publication-title: J Med Chem doi: 10.1021/acs.jmedchem.7b01261 – volume: 4 year: 2018 ident: CR32 article-title: Cyclin E1 and Rb modulation as common events at time of resistance to palbociclib in hormone receptor-positive breast cancer publication-title: NPJ Breast Cancer doi: 10.1038/s41523-018-0092-4 – volume: 12 start-page: 356 year: 2022 end-page: 71 ident: CR16 article-title: INK4 Tumor Suppressor Proteins Mediate Resistance to CDK4/6 Kinase Inhibitors publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-20-1726 – volume: 458 start-page: 732 year: 2009 end-page: 6 ident: CR30 article-title: An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer publication-title: Nature. doi: 10.1038/nature07884 – volume: 226 start-page: 113849 year: 2021 ident: CR45 article-title: AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss publication-title: Eur J Med Chem doi: 10.1016/j.ejmech.2021.113849 – volume: 569 start-page: 560 year: 2019 end-page: 4 ident: CR11 article-title: Genomic characterization of metastatic breast cancers publication-title: Nature. doi: 10.1038/s41586-019-1056-z – volume: 11 start-page: 580251 year: 2020 ident: CR34 article-title: Mechanisms of CDK4/6 Inhibitor Resistance in Luminal Breast Cancer publication-title: Front Pharmacol doi: 10.3389/fphar.2020.580251 – volume: 124 start-page: 13 year: 2014 end-page: 23 ident: CR19 article-title: Requirement for CDK6 in MLL-rearranged acute myeloid leukemia publication-title: Blood. doi: 10.1182/blood-2014-02-558114 – volume: 362 start-page: eaat0572 year: 2018 ident: CR29 article-title: Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN publication-title: Science. doi: 10.1126/science.aat0572 – volume: 592 start-page: 789 year: 2021 end-page: 93 ident: CR6 article-title: CRL4(AMBRA1) is a master regulator of D-type cyclins publication-title: Nature. doi: 10.1038/s41586-021-03445-y – volume: 81 start-page: 1347 year: 2021 end-page: 60 ident: CR15 article-title: Functional Determinants of Cell Cycle Plasticity and Sensitivity to CDK4/6 Inhibition publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-20-2275 – volume: 70 start-page: 127 year: 2021 end-page: 38 ident: CR36 article-title: Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer publication-title: Gut. doi: 10.1136/gutjnl-2020-321000 – volume: 6 start-page: pl1 year: 2013 ident: CR9 article-title: Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal publication-title: Sci Signal doi: 10.1126/scisignal.2004088 – volume: 8 year: 2020 ident: CR28 article-title: Novel immunomodulatory drugs and neo-substrates publication-title: Biomark Res doi: 10.1186/s40364-020-0182-y – volume: 36 start-page: 2255 year: 2017 end-page: 64 ident: CR33 article-title: Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence publication-title: Oncogene. doi: 10.1038/onc.2016.379 – volume: 73 start-page: 1059 year: 1993 end-page: 65 ident: CR2 article-title: Mammalian G1 cyclins publication-title: Cell. doi: 10.1016/0092-8674(93)90636-5 – volume: 12 year: 2021 ident: CR18 article-title: Clinical CDK4/6 inhibitors induce selective and immediate dissociation of p21 from cyclin D-CDK4 to inhibit CDK2 publication-title: Nat Commun doi: 10.1038/s41467-021-23612-z – volume: 592 start-page: 794 year: 2021 end-page: 8 ident: CR7 article-title: The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D publication-title: Nature. doi: 10.1038/s41586-021-03474-7 – volume: 48 start-page: 2388 year: 2005 end-page: 406 ident: CR38 article-title: Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6 publication-title: J Med Chem doi: 10.1021/jm049354h – volume: 366 start-page: eaaw2106 year: 2019 ident: CR17 article-title: p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition publication-title: Science. doi: 10.1126/science.aaw2106 – volume: 55 start-page: 2704 year: 2019 end-page: 7 ident: CR25 article-title: PROTACs suppression of CDK4/6, crucial kinases for cell cycle regulation in cancer publication-title: Chem Commun (Camb) doi: 10.1039/C9CC00163H – volume: 39 start-page: 1404 year: 2021 end-page: 21.e11 ident: CR42 article-title: Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor publication-title: Cancer Cell doi: 10.1016/j.ccell.2021.08.009 – volume: 11 start-page: 693104 year: 2021 ident: CR37 article-title: Clinical and Pharmacologic Differences of CDK4/6 Inhibitors in Breast Cancer publication-title: Front Oncol doi: 10.3389/fonc.2021.693104 – volume: 41 start-page: 3524 year: 2022 end-page: 38 ident: CR10 article-title: RB loss determines selective resistance and novel vulnerabilities in ER-positive breast cancer models publication-title: Oncogene. doi: 10.1038/s41388-022-02362-2 – volume: 38 start-page: 110448 year: 2022 ident: CR22 article-title: CDK/cyclin dependencies define extreme cancer cell-cycle heterogeneity and collateral vulnerabilities publication-title: Cell Rep doi: 10.1016/j.celrep.2022.110448 – volume: 4 start-page: 64 year: 2019 ident: CR40 article-title: PROTACs: great opportunities for academia and industry publication-title: Signal Transduct Target Ther doi: 10.1038/s41392-019-0101-6 – volume: 45 start-page: 129 year: 2016 end-page: 38 ident: CR13 article-title: Targeting CDK4/6 in patients with cancer publication-title: Cancer Treat Rev doi: 10.1016/j.ctrv.2016.03.002 – volume: 58 start-page: 6321 year: 2019 end-page: 6 ident: CR24 article-title: Development of Dual and Selective Degraders of Cyclin-Dependent Kinases 4 and 6 publication-title: Angew Chem Int Ed Engl doi: 10.1002/anie.201901336 – volume: 16 start-page: 101 year: 2017 end-page: 14 ident: CR23 article-title: Induced protein degradation: an emerging drug discovery paradigm publication-title: Nat Rev Drug Discov doi: 10.1038/nrd.2016.211 – volume: 14 start-page: 1255 year: 2019 end-page: 68 ident: CR39 article-title: PROTACs- a game-changing technology publication-title: Expert Opin Drug Discov doi: 10.1080/17460441.2019.1659242 – volume: 6 start-page: eabb2210 year: 2020 ident: CR41 article-title: Increased lysosomal biomass is responsible for the resistance of triple-negative breast cancers to CDK4/6 inhibition publication-title: Sci Adv doi: 10.1126/sciadv.abb2210 – volume: 24 year: 2022 ident: CR8 article-title: Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer publication-title: Breast Cancer Res doi: 10.1186/s13058-022-01510-6 – volume: 6 start-page: e2100002 year: 2022 ident: CR12 article-title: Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer publication-title: JCO Precis Oncol doi: 10.1200/PO.21.00002 – volume: 37 start-page: 514 year: 2020 end-page: 29 ident: CR20 article-title: Mechanisms of Sensitivity and Resistance to CDK4/6 Inhibition publication-title: Cancer Cell doi: 10.1016/j.ccell.2020.03.010 – volume: 59 start-page: 13865 year: 2020 end-page: 70 ident: CR44 article-title: Development of CDK2 and CDK5 Dual Degrader TMX-2172 publication-title: Angew Chem Int Ed Engl doi: 10.1002/anie.202004087 – volume: 38 start-page: 3355 year: 2019 end-page: 70 ident: CR14 article-title: Cell cycle plasticity driven by MTOR signaling: integral resistance to CDK4/6 inhibition in patient-derived models of pancreatic cancer publication-title: Oncogene. doi: 10.1038/s41388-018-0650-0 – volume: 23 start-page: 74 year: 2022 end-page: 88 ident: CR1 article-title: Cell cycle control in cancer publication-title: Nat Rev Mol Cell Biol doi: 10.1038/s41580-021-00404-3 – volume: 82 start-page: 2171 year: 2022 end-page: 84 ident: CR35 article-title: Functional Genomic Analysis of CDK4 and CDK6 Gene Dependency across Human Cancer Cell Lines publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-21-2428 – volume: 535 start-page: 252 year: 2016 end-page: 7 ident: CR27 article-title: A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase publication-title: Nature. doi: 10.1038/nature18611 – volume: 34 start-page: 893 year: 2018 end-page: 905.e8 ident: CR31 article-title: Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway publication-title: Cancer Cell doi: 10.1016/j.ccell.2018.11.006 – volume: 127 start-page: 2072 year: 2022 end-page: 85 ident: CR43 article-title: Concurrent inhibition of CDK2 adds to the anti-tumour activity of CDK4/6 inhibition in GIST publication-title: Br J Cancer doi: 10.1038/s41416-022-01990-5 – volume: 15 start-page: 4215 year: 1995 end-page: 24 ident: CR4 article-title: Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes publication-title: Mol Cell Biol doi: 10.1128/MCB.15.8.4215 – volume: 17 start-page: 1871 year: 2018 end-page: 85 ident: CR5 article-title: Targeting the cell cycle in breast cancer: towards the next phase publication-title: Cell Cycle doi: 10.1080/15384101.2018.1502567 – volume: 458 start-page: 732 year: 2009 ident: 2399_CR30 publication-title: Nature. doi: 10.1038/nature07884 – volume: 36 start-page: 2255 year: 2017 ident: 2399_CR33 publication-title: Oncogene. doi: 10.1038/onc.2016.379 – volume: 124 start-page: 13 year: 2014 ident: 2399_CR19 publication-title: Blood. doi: 10.1182/blood-2014-02-558114 – volume: 14 start-page: 1255 year: 2019 ident: 2399_CR39 publication-title: Expert Opin Drug Discov doi: 10.1080/17460441.2019.1659242 – volume: 11 start-page: 580251 year: 2020 ident: 2399_CR34 publication-title: Front Pharmacol doi: 10.3389/fphar.2020.580251 – volume: 58 start-page: 6321 year: 2019 ident: 2399_CR24 publication-title: Angew Chem Int Ed Engl doi: 10.1002/anie.201901336 – volume: 70 start-page: 127 year: 2021 ident: 2399_CR36 publication-title: Gut. doi: 10.1136/gutjnl-2020-321000 – volume: 37 start-page: 514 year: 2020 ident: 2399_CR20 publication-title: Cancer Cell doi: 10.1016/j.ccell.2020.03.010 – volume: 24 year: 2022 ident: 2399_CR8 publication-title: Breast Cancer Res doi: 10.1186/s13058-022-01510-6 – volume: 55 start-page: 2704 year: 2019 ident: 2399_CR25 publication-title: Chem Commun (Camb) doi: 10.1039/C9CC00163H – volume: 362 start-page: eaat0572 year: 2018 ident: 2399_CR29 publication-title: Science. doi: 10.1126/science.aat0572 – volume: 81 start-page: 1347 year: 2021 ident: 2399_CR15 publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-20-2275 – volume: 592 start-page: 789 year: 2021 ident: 2399_CR6 publication-title: Nature. doi: 10.1038/s41586-021-03445-y – volume: 4 year: 2018 ident: 2399_CR32 publication-title: NPJ Breast Cancer doi: 10.1038/s41523-018-0092-4 – volume: 23 start-page: 74 year: 2022 ident: 2399_CR1 publication-title: Nat Rev Mol Cell Biol doi: 10.1038/s41580-021-00404-3 – volume: 38 start-page: 110448 year: 2022 ident: 2399_CR22 publication-title: Cell Rep doi: 10.1016/j.celrep.2022.110448 – volume: 11 start-page: 693104 year: 2021 ident: 2399_CR37 publication-title: Front Oncol doi: 10.3389/fonc.2021.693104 – volume: 366 start-page: eaaw2106 year: 2019 ident: 2399_CR17 publication-title: Science. doi: 10.1126/science.aaw2106 – volume: 34 start-page: 893 year: 2018 ident: 2399_CR31 publication-title: Cancer Cell doi: 10.1016/j.ccell.2018.11.006 – volume: 13 start-page: 1501 year: 1999 ident: 2399_CR3 publication-title: Genes Dev doi: 10.1101/gad.13.12.1501 – volume: 45 start-page: 129 year: 2016 ident: 2399_CR13 publication-title: Cancer Treat Rev doi: 10.1016/j.ctrv.2016.03.002 – volume: 61 start-page: 1499 year: 2018 ident: 2399_CR26 publication-title: J Med Chem doi: 10.1021/acs.jmedchem.7b01261 – volume: 4 start-page: 64 year: 2019 ident: 2399_CR40 publication-title: Signal Transduct Target Ther doi: 10.1038/s41392-019-0101-6 – volume: 592 start-page: 794 year: 2021 ident: 2399_CR7 publication-title: Nature. doi: 10.1038/s41586-021-03474-7 – volume: 38 start-page: 3355 year: 2019 ident: 2399_CR14 publication-title: Oncogene. doi: 10.1038/s41388-018-0650-0 – volume: 6 start-page: eabb2210 year: 2020 ident: 2399_CR41 publication-title: Sci Adv doi: 10.1126/sciadv.abb2210 – volume: 127 start-page: 2072 year: 2022 ident: 2399_CR43 publication-title: Br J Cancer doi: 10.1038/s41416-022-01990-5 – volume: 569 start-page: 560 year: 2019 ident: 2399_CR11 publication-title: Nature. doi: 10.1038/s41586-019-1056-z – volume: 8 year: 2020 ident: 2399_CR28 publication-title: Biomark Res doi: 10.1186/s40364-020-0182-y – volume: 226 start-page: 113849 year: 2021 ident: 2399_CR45 publication-title: Eur J Med Chem doi: 10.1016/j.ejmech.2021.113849 – volume: 6 start-page: e2100002 year: 2022 ident: 2399_CR12 publication-title: JCO Precis Oncol doi: 10.1200/PO.21.00002 – volume: 41 start-page: 3524 year: 2022 ident: 2399_CR10 publication-title: Oncogene. doi: 10.1038/s41388-022-02362-2 – volume: 15 start-page: 4215 year: 1995 ident: 2399_CR4 publication-title: Mol Cell Biol doi: 10.1128/MCB.15.8.4215 – volume: 16 start-page: 101 year: 2017 ident: 2399_CR23 publication-title: Nat Rev Drug Discov doi: 10.1038/nrd.2016.211 – volume: 73 start-page: 1059 year: 1993 ident: 2399_CR2 publication-title: Cell. doi: 10.1016/0092-8674(93)90636-5 – volume: 17 start-page: 1871 year: 2018 ident: 2399_CR5 publication-title: Cell Cycle doi: 10.1080/15384101.2018.1502567 – volume: 59 start-page: 13865 year: 2020 ident: 2399_CR44 publication-title: Angew Chem Int Ed Engl doi: 10.1002/anie.202004087 – volume: 12 start-page: 356 year: 2022 ident: 2399_CR16 publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-20-1726 – volume: 82 start-page: 2171 year: 2022 ident: 2399_CR35 publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-21-2428 – volume: 12 year: 2021 ident: 2399_CR18 publication-title: Nat Commun doi: 10.1038/s41467-021-23612-z – volume: 2 start-page: 429 year: 2021 ident: 2399_CR21 publication-title: Nat Cancer doi: 10.1038/s43018-021-00174-z – volume: 39 start-page: 1404 year: 2021 ident: 2399_CR42 publication-title: Cancer Cell doi: 10.1016/j.ccell.2021.08.009 – volume: 535 start-page: 252 year: 2016 ident: 2399_CR27 publication-title: Nature. doi: 10.1038/nature18611 – volume: 6 start-page: pl1 year: 2013 ident: 2399_CR9 publication-title: Sci Signal doi: 10.1126/scisignal.2004088 – volume: 48 start-page: 2388 year: 2005 ident: 2399_CR38 publication-title: J Med Chem doi: 10.1021/jm049354h
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Snippet	Background Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle.... Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We... BackgroundCyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle....
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StartPage	1238
SubjectTerms	631/337/505 631/92/436/434 Animals Biomedical and Life Sciences Biomedicine Cancer Research Cell activation Cell cycle Cell Cycle - drug effects Cell Line, Tumor Cell proliferation Cell Proliferation - drug effects Chimeras Cyclin E Cyclin-dependent kinase 2 Cyclin-dependent kinase 4 Cyclin-Dependent Kinase 4 - antagonists & inhibitors Cyclin-Dependent Kinase 4 - metabolism Cyclin-Dependent Kinase 6 - antagonists & inhibitors Cyclin-Dependent Kinase 6 - metabolism Cyclin-dependent kinases Drug Resistance Epidemiology Humans INK4a protein Kinases Mice Molecular Medicine Oncology Organoids p16 Protein Piperazines - pharmacology Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Proteolysis Proteolysis - drug effects Pyridines - chemistry Pyridines - pharmacology Thalidomide - analogs & derivatives Thalidomide - pharmacology Tumors Xenograft Model Antitumor Assays
Title	PROTAC-mediated CDK degradation differentially impacts cancer cell cycles due to heterogeneity in kinase dependencies
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