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Open Access 01-03-2021 | Glioblastoma | Non-Thematic Review

Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma—backbone or add-on in immune-oncology?

Authors: Christin Riess, Nina Irmscher, Inken Salewski, Daniel Strüder, Carl-Friedrich Classen, Christina Große-Thie, Christian Junghanss, Claudia Maletzki

Published in: Cancer and Metastasis Reviews | Issue 1/2021

Abstract

Cyclin-dependent kinases (CDK) control the cell cycle and play a crucial role in oncogenesis. Pharmacologic inhibition of CDK has contributed to the recent clinical approval of dual CDK4/6 inhibitors for the treatment of breast and small cell lung cancer. While the anticancer cell effects of CDK inhibitors are well-established, preclinical and early clinical studies describe additional mechanisms of action such as chemo- and radiosensitization or immune stimulation. The latter offers great potential to incorporate CDK inhibitors in immune-based treatments. However, dosing schedules and accurate timing of each combination partner need to be respected to prevent immune escape and resistance. In this review, we provide a detailed summary of CDK inhibitors in the two solid cancer types head and neck cancer and glioblastoma multiforme; it describes the molecular mechanisms of response vs. resistance and covers strategies to avoid resistance by the combination of immunotherapy or targeted therapy.

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Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013.CrossRefPubMed

Jardim, D. L., Millis, S. Z., Ross, J. S., Woo, M. S.-A., Ali, S. M., & Kurzrock, R. (2020). Cyclin pathway genomic alterations across 190,247 solid tumors: Leveraging large-scale data to inform therapeutic directions. Oncologist. https://doi.org/10.1634/theoncologist.2020-0509.

Economopoulou, P., Kotsantis, J., Psyrri, A. (2020). Special issue about head and neck cancers: HPV positive cancers. Review International Journal of Molecular Sciences, 21(9), 3388. https://doi.org/10.3390/ijms21093388.

Chong, Q.-Y., Kok, Z.-H., Bui, N.-L.-C., Xiang, X., Wong, A. L.-A., Yong, W.-P., et al. (2020). A unique CDK4/6 inhibitor: Current and future therapeutic strategies of abemaciclib. Pharmacological Research, 156, 104686. https://doi.org/10.1016/j.phrs.2020.104686.CrossRefPubMed

Cen, L., Carlson, B. L., Schroeder, M. A., Ostrem, J. L., Kitange, G. J., Mladek, A. C., et al. (2012). p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. Neuro-oncology, 14(7), 870–881. https://doi.org/10.1093/neuonc/nos114.CrossRefPubMedPubMedCentral

Wiedemeyer, W. R., Dunn, I. F., Quayle, S. N., Zhang, J., Chheda, M. G., Dunn, G. P., et al. (2010). Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM. Proceedings of the National Academy of Sciences of the United States of America, 107(25), 11501–11506. https://doi.org/10.1073/pnas.1001613107.CrossRefPubMedPubMedCentral

Cemeli, T., Guasch-Vallés, M., Nàger, M., Felip, I., Cambray, S., Santacana, M., et al. (2019). Cytoplasmic cyclin D1 regulates glioblastoma dissemination. The Journal of Pathology, 248(4), 501–513. https://doi.org/10.1002/path.5277.CrossRefPubMed

Chen, X., Pan, Y., Yan, M., Bao, G., & Sun, X. (2020). Identification of potential crucial genes and molecular mechanisms in glioblastoma multiforme by bioinformatics analysis. Molecular Medicine Reports, 22(2), 859–869. https://doi.org/10.3892/mmr.2020.11160.CrossRefPubMedPubMedCentral

Han, B. A., Yang, X. P., Hosseini, D. K., Zhang, P., Zhang, Y., Yu, J. T., et al. (2020). Identification of candidate aberrantly methylated and differentially expressed genes in esophageal squamous cell carcinoma. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-66847-4.

10.

van Harten, A. M., Buijze, M., van der Mast, R., Rooimans, M. A., Martens-de Kemp, S. R., Bachas, C., et al. (2019). Targeting the cell cycle in head and neck cancer by Chk1 inhibition: A novel concept of bimodal cell death. Oncogenesis, 8(7). https://doi.org/10.1038/s41389-019-0147-x.

11.

Gadhikar, M. A., Zhang, J., Shen, L., Rao, X., Wang, J., Zhao, M., et al. (2018). CDKN2A/p16 deletion in head and neck cancer cells is associated with cdk2 activation, replication stress, and vulnerability to CHK1 inhibition. Cancer Research, 78(3), 781–797. https://doi.org/10.1158/0008-5472.CAN-17-2802.CrossRefPubMed

12.

Soffar, A., Storch, K., Aleem, E., & Cordes, N. (2013). CDK2 knockdown enhances head and neck cancer cell radiosensitivity. International Journal of Radiation Biology, 89(7), 523–531. https://doi.org/10.3109/09553002.2013.782108.CrossRefPubMed

13.

Wang, J., Yang, T., Xu, G., Liu, H., Ren, C., Xie, W., & Wang, M. (2016). Cyclin-dependent kinase 2 promotes tumor proliferation and induces radio resistance in glioblastoma. Translational Oncology, 9(6), 548–556. https://doi.org/10.1016/j.tranon.2016.08.007.CrossRefPubMedPubMedCentral

14.

Li, H., Jiang, X., Yu, Y., Huang, W., Xing, H., Agar, N. Y., et al. (2015). KAP regulates ROCK2 and Cdk2 in an RNA-activated glioblastoma invasion pathway. Oncogene, 34(11), 1432–1441. https://doi.org/10.1038/onc.2014.49.CrossRefPubMed

15.

Bellail, A. C., Olson, J. J., & Hao, C. (2014). SUMO1 modification stabilizes CDK6 protein and drives the cell cycle and glioblastoma progression. Nature Communications, 5. https://doi.org/10.1038/ncomms5234.

16.

Zhong, S., Wu, B., Dong, X., Han, Y., Jiang, S., Zhang, Y., et al. (2018). Identification of driver genes and key pathways of glioblastoma shows JNJ-7706621 as a novel antiglioblastoma drug. World Neurosurgery, 109, e329–e342. https://doi.org/10.1016/j.wneu.2017.09.176.CrossRefPubMed

17.

Premkumar, D. R., Jane, E. P., Thambireddy, S., Sutera, P. A., Cavaleri, J. M., & Pollack, I. F. (2018). Mitochondrial dysfunction RAD51, and Ku80 proteolysis promote apoptotic effects of Dinaciclib in Bcl-xL silenced cells. Molecular Carcinogenesis, 57(4), 469–482. https://doi.org/10.1002/mc.22771.CrossRefPubMed

18.

Patel, V., Jakus, J., Harris, C. M., Ensley, J. F., Robbins, K. C., & Yeudall, W. A. (1997). Altered expression and activity of G1/S cyclins and cyclin-dependent kinases characterize squamous cell carcinomas of the head and neck. International Journal of Cancer, 73(4), 551–555. https://doi.org/10.1002/(SICI)1097-0215(19971114)73:4<551::AID-IJC16>3.0.CO;2-C.CrossRefPubMed

19.

Göttgens, E. L., Bussink, J., Leszczynska, K. B., Peters, H., Span, P. N., & Hammond, E. M. (2019). Inhibition of CDK4/CDK6 enhances radiosensitivity of HPV negative head and neck squamous cell carcinomas. International Journal of Radiation Oncology Biology Physics, 105(3), 548–558. https://doi.org/10.1016/j.ijrobp.2019.06.2531.CrossRef

20.

Shapiro, G. I. (2006, April 10). Cyclin-dependent kinase pathways as targets for cancer treatment. Journal of Clinical Oncology. https://doi.org/10.1200/JCO.2005.03.7689.

21.

Billard-Sandu, C., Tao, Y. G., Sablin, M. P., Dumitrescu, G., Billard, D., & Deutsch, E. (2020, May). CDK4/6 inhibitors in P16/HPV16-negative squamous cell carcinoma of the head and neck. European Archives of Oto-Rhino-Laryngology. Springer. https://doi.org/10.1007/s00405-020-05891-2.

22.

Herrera-Abreu, M. T., Palafox, M., Asghar, U., Rivas, M. A., Cutts, R. J., Garcia-Murillas, I., et al. (2016). Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer. Cancer Research, 76(8), 2301–2313. https://doi.org/10.1158/0008-5472.CAN-15-0728.CrossRefPubMedPubMedCentral

23.

Condorelli, R., Spring, L., O’Shaughnessy, J., Lacroix, L., Bailleux, C., Scott, V., et al. (2018). Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer. Annals of Oncology, 29(3), 640–645. https://doi.org/10.1093/annonc/mdx784.CrossRefPubMed

24.

Karamboulas, C., Bruce, J. P., Hope, A. J., Meens, J., Huang, S. H., Erdmann, N., et al. (2018). Patient-derived xenografts for prognostication and personalized treatment for head and neck squamous cell carcinoma. Cell Reports, 25(5), 1318–1331.e4. https://doi.org/10.1016/j.celrep.2018.10.004.CrossRefPubMed

25.

Ku, B. M., Yi, S. Y., Koh, J., Bae, Y. H., Sun, J. M., Lee, S. H., et al. (2016). The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma. Oncotarget, 7(12), 14803–14813. https://doi.org/10.18632/oncotarget.7543.CrossRefPubMedPubMedCentral

26.

van Caloen, G., Schmitz, S., El Baroudi, M., Caignet, X., Pyr dit Ruys, S., Roger, P. P., et al. (2020). Preclinical activity of ribociclib in squamous cell carcinoma of the head and neck. Molecular Cancer Therapeutics, 19(3), 777–789. https://doi.org/10.1158/1535-7163.MCT-19-0695.CrossRefPubMed

27.

Xie, X., Zheng, W., Chen, T., Lin, W., Liao, Z., Liu, J., & Ding, Y. (2019). CDK4/6 inhibitor palbociclib amplifies the radiosensitivity to nasopharyngeal carcinoma cells via mediating apoptosis and suppressing DNA damage repair. Oncotargets and Therapy, 12, 11107–11117. https://doi.org/10.2147/OTT.S234221.CrossRefPubMedPubMedCentral

28.

Tai, T. S., Lin, P. M., Wu, C. F., Hung, S. K., Huang, C. I., Wang, C. C., & Su, Y. C. (2019). CDK4/6 inhibitor LEE011 is a potential radiation-sensitizer in head and neck squamous cell carcinoma: An in vitro study. Anticancer Research, 39(2), 713–720. https://doi.org/10.21873/anticanres.13167.CrossRefPubMed

29.

Robinson, A. M., Rathore, R., Redlich, N. J., Adkins, D. R., VanArsdale, T., Van Tine, B. A., & Michel, L. S. (2019). Cisplatin exposure causes c-Myc-dependent resistance to CDK4/6 inhibition in HPV-negative head and neck squamous cell carcinoma. Cell Death & Disease, 10(11), 867. https://doi.org/10.1038/s41419-019-2098-8.CrossRef

30.

Michel, L., Ley, J., Wildes, T. M., Schaffer, A., Robinson, A., Chun, S. E., et al. (2016). Phase i trial of palbociclib, a selective cyclin dependent kinase 4/6 inhibitor, in combination with cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Oral Oncology, 58, 41–48. https://doi.org/10.1016/j.oraloncology.2016.05.011.CrossRefPubMedPubMedCentral

31.

Adkins, D., Ley, J., Neupane, P., Worden, F., Sacco, A. G., Palka, K., et al. (2019). Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: A multicentre, multigroup, phase 2 trial. The Lancet Oncology, 20(9), 1295–1305. https://doi.org/10.1016/S1470-2045(19)30405-X.CrossRefPubMed

32.

Swiecicki, P. L., Durm, G., Bellile, E., Bhangale, A., Brenner, J. C., & Worden, F. P. (2020). A multi-center phase II trial evaluating the efficacy of palbociclib in combination with carboplatin for the treatment of unresectable recurrent or metastatic head and neck squamous cell carcinoma. Investigational New Drugs, 38(5). https://doi.org/10.1007/s10637-020-00898-2.

33.

Michaud, K., Solomon, D. A., Oermann, E., Kim, J. S., Zhong, W. Z., Prados, M. D., et al. (2010). Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts. Cancer Research, 70(8), 3228–3238. https://doi.org/10.1158/0008-5472.CAN-09-4559.CrossRefPubMedPubMedCentral

34.

Hashizume, R., Zhang, A., Mueller, S., Prados, M. D., Lulla, R. R., Goldman, S., et al. (2016). Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth. Neuro-oncology, 18(11), 1519–1528. https://doi.org/10.1093/neuonc/now106.CrossRefPubMedPubMedCentral

35.

Whittaker, S., Madani, D., Joshi, S., Chung, S. A., Johns, T., Day, B., et al. (2017). Combination of palbociclib and radiotherapy for glioblastoma. Cell Death Discovery, 3(1). https://doi.org/10.1038/cddiscovery.2017.33.

36.

Taylor, J. W., Parikh, M., Phillips, J. J., James, C. D., Molinaro, A. M., Butowski, N. A., et al. (2018). Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma. Journal of Neuro-Oncology, 140(2). https://doi.org/10.1007/s11060-018-2977-3.

37.

Morris-Hanon, O., Marazita, M. C., Romorini, L., Isaja, L., Fernandez-Espinosa, D. D., Sevlever, G. E., et al. (2019). Palbociclib effectively halts proliferation but fails to induce senescence in patient-derived glioma stem cells. Molecular Neurobiology, 56(11), 7810–7821. https://doi.org/10.1007/s12035-019-1633-z.CrossRefPubMed

38.

Li, M., Xiao, A., Floyd, D., Olmez, I., Lee, J., Godlewski, J., et al. (2017). CDK4/6 inhibition is more active against the glioblastoma proneural subtype. Oncotarget, 8(33), 55319–55331. https://doi.org/10.18632/oncotarget.19429.CrossRefPubMedPubMedCentral

39.

Shi, J., Lv, S., Wu, M., Wang, X., Deng, Y., Li, Y., et al. (2020). HOTAIR-EZH2 inhibitor AC1Q3QWB upregulates CWF19L1 and enhances cell cycle inhibition of CDK4/6 inhibitor palbociclib in glioma. Clinical and Translational Medicine, 10(1), 182–198. https://doi.org/10.1002/ctm2.21.CrossRefPubMedPubMedCentral

40.

Sun, Y., Sun, Y., Yan, K., Li, Z., Xu, C., Geng, Y., et al. (2019). Potent anti-tumor efficacy of palbociclib in treatment-naïve H3.3K27M-mutant diffuse intrinsic pontine glioma. EBioMedicine, 43, 171–179. https://doi.org/10.1016/j.ebiom.2019.04.043.CrossRefPubMedPubMedCentral

41.

Patel, Y. T., Davis, A., Baker, S. J., Campagne, O., & Stewart, C. F. (2019). CNS penetration of the CDK4/6 inhibitor ribociclib in non-tumor bearing mice and mice bearing pediatric brain tumors. Cancer Chemotherapy and Pharmacology, 84(2), 447–452. https://doi.org/10.1007/s00280-019-03864-9.CrossRefPubMedPubMedCentral

42.

Tien, A. C., Li, J., Bao, X., Derogatis, A., Kim, S., Mehta, S., & Sanai, N. (2019). A phase 0 trial of ribociclib in recurrent glioblastoma patients incorporating a tumor pharmacodynamic- and pharmacokinetic-guided expansion cohort. Clinical Cancer Research, 25(19), 5777–5786. https://doi.org/10.1158/1078-0432.CCR-19-0133.CrossRefPubMedPubMedCentral

43.

Miller, T. W., Traphagen, N. A., Li, J., Lewis, L. D., Lopes, B., Asthagiri, A., Loomba, J., de Jong, J., Schiff, D., Patel, S. H., Purow, B. W., & Fadul, C. E. (2019). Tumor pharmacokinetics and pharmacodynamics of the CDK4/6 inhibitor ribociclib in patients with recurrent glioblastoma. Journal of Neuro-Oncology, 144(3), 563–572. https://doi.org/10.1007/s11060-019-03258-0.CrossRefPubMedPubMedCentral

44.

Poratti, M., & Marzaro, G. (2019, June 15). Third-generation CDK inhibitors: A review on the synthesis and binding modes of palbociclib, ribociclib and abemaciclib. European Journal of Medicinal Chemistry. Elsevier Masson SAS. https://doi.org/10.1016/j.ejmech.2019.03.064.

45.

Wu, T., Chen, Z., To, K. K. W, Fang, X., Wang, F., Cheng, B., & Fu, L. (2017). Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochemical Pharmacology, 124, 29–42. https://doi.org/10.1016/j.bcp.2016.10.015.CrossRefPubMed

46.

Hino, H., Iriyama, N., Kokuba, H., Kazama, H., Moriya, S., Takano, N., et al. (2020). Abemaciclib induces atypical cell death in cancer cells characterized by formation of cytoplasmic vacuoles derived from lysosomes. Cancer Science, 111(6), 2132–2145. https://doi.org/10.1111/cas.14419.CrossRefPubMedPubMedCentral

47.

Riess, C., Schneider, B., Kehnscherper, H., Gesche, J., Irmscher, N., Shokraie, F., et al. (2020). Activation of the kynurenine pathway in human malignancies can be suppressed by the cyclin-dependent kinase inhibitor dinaciclib. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.00055.

48.

Raub, T. J., Wishart, G. N., Kulanthaivel, P., Staton, B. A., Ajamie, R. T., Sawada, G. A., et al. (2015). Brain exposure of two selective dual CDK4 and CDK6 inhibitors and the antitumor activity of CDK4 and CDK6 inhibition in combination with temozolomide in an intracranial glioblastoma xenograft. Drug Metabolism and Disposition, 43(9), 1360–1371. https://doi.org/10.1124/dmd.114.062745.CrossRefPubMed

49.

Patnaik, A., Rosen, L. S., Tolaney, S. M., Tolcher, A. W., Goldman, J. W., Gandhi, L., et al. (2016). Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non–small cell lung cancer, and other solid tumors. Cancer Discovery, 6(7), 740–753. https://doi.org/10.1158/2159-8290.CD-16-0095.CrossRefPubMed

50.

Diab, S., Yu, M., & Wang, S. (2020, July 23). CDK7 inhibitors in cancer therapy: The sweet smell of success? Journal of Medicinal Chemistry, American Chemical Society. https://doi.org/10.1021/acs.jmedchem.9b01985.

51.

Martin, R. D., Hébert, T. E., & Tanny, J. C. (2020, May 1). Therapeutic targeting of the general RNA polymerase II transcription machinery. International Journal of Molecular Sciences. MDPI AG. https://doi.org/10.3390/ijms21093354.

52.

Fan, Z., Devlin, J. R., Hogg, S. J., Doyle, M. A., Harrison, P. F., Todorovski, I., et al. (2020). CDK13 cooperates with CDK12 to control global RNA polymerase II processivity. Science Advances, 6(18). https://doi.org/10.1126/sciadv.aaz5041.

53.

Hu, S., Marineau, J. J., Rajagopal, N., Hamman, K. B., Choi, Y. J., Schmidt, D. R., et al. (2019). Discovery and characterization of SY-1365, a selective, covalent inhibitor of CDK7. Cancer Research, 79(13), 3479–3491. https://doi.org/10.1158/0008-5472.CAN-19-0119.CrossRefPubMed

54.

Ow, T. J., Fulcher, C. D., Thomas, C., Broin, P., López, A., Reyna, D. E., et al. (2019). Optimal targeting of BCL-family proteins in head and neck squamous cell carcinoma requires inhibition of both BCL-xL and MCL-1. Oncotarget, 10(4), 494–510. https://doi.org/10.18632/oncotarget.26563.CrossRefPubMedPubMedCentral

55.

Yuan, J., Jiang, Y. Y., Mayakonda, A., Huang, M., Ding, L. W., Lin, H., et al. (2017). Super-enhancers promote transcriptional dysregulation in nasopharyngeal carcinoma. Cancer Research, 77(23), 6614–6626. https://doi.org/10.1158/0008-5472.CAN-17-1143.CrossRefPubMedPubMedCentral

56.

Pott, S., & Lieb, J. D. (2015). What are super-enhancers? Nature Genetics. Nature Publishing Group. https://doi.org/10.1038/ng.3167.

57.

Zhang, W., Ge, H., Jiang, Y., Huang, R., Wu, Y., Wang, D., et al. (2020). Combinational therapeutic targeting of BRD4 and CDK7 synergistically induces anticancer effects in head and neck squamous cell carcinoma. Cancer Letters, 469, 510–523. https://doi.org/10.1016/j.canlet.2019.11.027.CrossRefPubMed

58.

Meng, W., Wang, J., Wang, B., Liu, F., Li, M., Zhao, Y., et al. (2018). CDK7 inhibition is a novel therapeutic strategy against GBM both in vitro and in vivo. Cancer Management and Research, 10, 5747–5758. https://doi.org/10.2147/CMAR.S183696.CrossRefPubMedPubMedCentral

59.

Garriga, J., & Graña, X. (2014). CDK9 inhibition strategy defines distinct sets of target genes. BMC Research Notes, 7(1). https://doi.org/10.1186/1756-0500-7-301.

60.

Cao, S., Yu, Y., Chen, S., Lei, D., Wang, S., Pan, X., & Peng, J. (2017). Inhibition of CDK9 induces apoptosis and potentiates the effect of cisplatin in hypopharyngeal carcinoma cells. Biochemical and Biophysical Research Communications, 482(4), 536–541. https://doi.org/10.1016/j.bbrc.2016.11.049.CrossRefPubMed

61.

Storch, K., & Cordes, N. (2016). The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells. International Journal of Oncology, 48(1), 191–198. https://doi.org/10.3892/ijo.2015.3246.CrossRefPubMed

62.

Su, Y. T., Chen, R., Wang, H., Song, H., Zhang, Q., Chen, L. Y., et al. (2018). Novel targeting of transcription and metabolism in glioblastoma. Clinical Cancer Research, 24(5), 1124–1137. https://doi.org/10.1158/1078-0432.CCR-17-2032.CrossRefPubMed

63.

Le Rhun, E., von Achenbach, C., Lohmann, B., Silginer, M., Schneider, H., Meetze, K., et al. (2019). Profound, durable and MGMT-independent sensitivity of glioblastoma cells to cyclin-dependent kinase inhibition. International Journal of Cancer, 145(1), 242–253. https://doi.org/10.1002/ijc.32069.CrossRefPubMed

64.

Erbayraktar, Z., Alural, B., Erbayraktar, R. S., & Erkan, E. P. (2016). Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness. Cancer Cell International, 16(1). https://doi.org/10.1186/s12935-016-0364-8.

65.

Lohmann, B., Le Rhun, E., Silginer, M., Epskamp, M., & Weller, M. (2020). Interferon-β sensitizes human glioblastoma cells to the cyclin-dependent kinase inhibitor, TG02. Oncology Letters, 19(4), 2649–2656. https://doi.org/10.3892/ol.2020.11362.CrossRefPubMedPubMedCentral

66.

Ziemann, F., Seltzsam, S., Dreffke, K., Preising, S., Arenz, A., Subtil, F. S. B., et al. (2017). Roscovitine strongly enhances the effect of olaparib on radiosensitivity for HPV neg. but not for HPV pos. HNSCC cell lines. Oncotarget, 8(62), 105170–105183. https://doi.org/10.18632/oncotarget.22005.CrossRefPubMedPubMedCentral

67.

Noonan, J. J., Jarzabek, M., Lincoln, F. A., Cavanagh, B. L., Pariag, A. R., Juric, V., et al. (2019). Implementing patient-derived xenografts to assess the effectiveness of cyclin-dependent kinase inhibitors in glioblastoma. Cancers, 11(12). https://doi.org/10.3390/cancers11122005.

68.

Yakisich, J. S., Boethius, J., Lindblom, I. O., Wallstedt, L., Vargas, V. I., Sidén, Å., & Cruz, M. H. (1999). Inhibition of DNA synthesis in human gliomas by roscovitine. NeuroReport, 10(12), 2563–2567. https://doi.org/10.1097/00001756-199908200-00023.CrossRefPubMed

69.

Kim, E. H., Kim, S. U., Shin, D. Y., & Choi, K. S. (2004). Roscovitine sensitizes glioma cells to TRAIL-mediated apoptosis by downregulation of survivin and XIAP. Oncogene, 23(2), 446–456. https://doi.org/10.1038/sj.onc.1207025.CrossRefPubMed

70.

Cheng, C. K., Gustafson, W. C., Charron, E., Houseman, B. T., Zunder, E., Goga, A., et al. (2012). Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma. Proceedings of the National Academy of Sciences of the United States of America, 109(31), 12722–12727. https://doi.org/10.1073/pnas.1202492109.CrossRefPubMedPubMedCentral

71.

Xi, M., Chen, T., Wu, C., Gao, X., Wu, Y., Luo, X., et al. (2019, February 15). CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors. European Journal of Medicinal Chemistry. Elsevier Masson SAS. https://doi.org/10.1016/j.ejmech.2018.11.076.

72.

Colella, B., Faienza, F., Carinci, M., D’Alessandro, G., Catalano, M., Santoro, A., et al. (2019). Autophagy induction impairs Wnt/β-catenin signalling through β-catenin relocalisation in glioblastoma cells. Cellular Signalling, 53, 357–364. https://doi.org/10.1016/j.cellsig.2018.10.017.CrossRefPubMed

73.

Li, M. H., Zhao, X. D., Liu, Y., An, J., Xiao, H., & Wang, C. (2017). Aberrant expression of CDK8 regulates the malignant phenotype and associated with poor prognosis in human laryngeal squamous cell carcinoma. European Archives of Oto-Rhino-Laryngology, 274(5), 2205–2213. https://doi.org/10.1007/s00405-017-4484-0.CrossRefPubMed

74.

Patel, V., Senderowicz, A. M., Pinto, D., Igishi, T., Raffeld, M., Quintanilla-Martinez, L., et al. (1998). Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis. Journal of Clinical Investigation, 102(9), 1674–1681. https://doi.org/10.1172/JCI3661.CrossRefPubMedCentral

75.

Dickson, M. A. (2014). Molecular pathways: CDK4 inhibitors for cancer therapy. Clinical Cancer Research, 20(13), 3379–3383. https://doi.org/10.1158/1078-0432.CCR-13-1551.CrossRefPubMed

76.

Senderowicz, A. M., Headlee, D., Stinson, S. F., Lush, R. M., Kalil, N., Villalba, L., et al. (1998). Phase I trial of continuous infusion flavopiridol, a novel cyclin- dependent kinase inhibitor, in patients with refractory neoplasms. Journal of Clinical Oncology, 16(9), 2986–2999. https://doi.org/10.1200/JCO.1998.16.9.2986.CrossRefPubMed

77.

Mihara, M., Shintani, S., Kiyota, A., Matsumura, T., & Wong, D. T. W. (2002). Cyclin-dependent kinase inhibitor (roscovitine) suppresses growth and induces apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells. International Journal of Oncology, 21(1), 95–101. https://doi.org/10.3892/ijo.21.1.95.CrossRefPubMed

78.

Hsieh, W.-S., Soo, R., Peh, B.-K., Loh, T., Dong, D., Soh, D., et al. (2009). Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 15(4), 1435–1442. https://doi.org/10.1158/1078-0432.CCR-08-1748.CrossRef

79.

Hau, P. M., Lung, H. L., Wu, M., Tsang, C. M., Wong, K. L., Mak, N. K., & Lo, K. W. (2020, May 14). Targeting Epstein-Barr virus in nasopharyngeal carcinoma. Frontiers in Oncology. Frontiers Media S.A. https://doi.org/10.3389/fonc.2020.00600.

80.

Gary, C., Hajek, M., Biktasova, A., Bellinger, G., Yarbrough, W. G., & Issaeva, N. (2016). Selective antitumor activity of roscovitine in head and neck cancer. Oncotarget, 7(25), 38598–38611. https://doi.org/10.18632/oncotarget.9560.CrossRefPubMedPubMedCentral

81.

Kolodziej, M., Goetz, C., Di Fazio, P., Montalbano, R., Ocker, M., Strik, H., & Quint, K. (2015). Roscovitine has anti-proliferative and pro-apoptotic effects on glioblastoma cell lines: A pilot study. Oncology Reports, 34(3), 1549–1556. https://doi.org/10.3892/or.2015.4105.CrossRefPubMed

82.

Pandey, V., Ranjan, N., Narne, P., & Babu, P. P. (2019). Roscovitine effectively enhances antitumor activity of temozolomide in vitro and in vivo mediated by increased autophagy and Caspase-3 dependent apoptosis. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-41380-1.

83.

Dolman, M. E. M., Poon, E., Ebus, M. E., Den Hartog, I. J. M., Van Noesel, C. J. M., Jamin, Y., et al. (2015). Cyclin-dependent kinase inhibitor AT7519 as a potential drug for MYCN-dependent neuroblastoma. Clinical Cancer Research, 21(22), 5100–5109. https://doi.org/10.1158/1078-0432.CCR-15-0313.CrossRefPubMedPubMedCentral

84.

Nutley, B. P., Raynaud, F. I., Wilson, S. C., Fischer, P. M., Hayes, A., Goddard, P. M., et al. (2005). Metabolism and pharmacokinetics of the cyclin-dependent kinase inhibitor R-roscovitine in the mouse. Molecular Cancer Therapeutics, 4(1), 125–139.PubMed

85.

Wei, X., Nian, J., Zheng, J., He, Y., & Zeng, M. (2020). Inhibition of cyclin-dependent kinases by AT7519 enhances nasopharyngeal carcinoma cell response to chemotherapy. Cancer Chemotherapy and Pharmacology. https://doi.org/10.1007/s00280-020-04068-2.

86.

Zhang, J., Lin, H., Jiang, H., Jiang, H., Xie, T., Wang, B., et al. (2020). A key genomic signature associated with lymphovascular invasion in head and neck squamous cell carcinoma. BMC Cancer, 20(1). https://doi.org/10.1186/s12885-020-06728-1.

87.

Syn, N. L., Lim, P. L., Kong, L. R., Wang, L., Wong, A. L.-A., Lim, C. M., et al. (2018). Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and xenograft models. Signal Transduction and Targeted Therapy, 3, 9. https://doi.org/10.1038/s41392-018-0010-0.CrossRefPubMedPubMedCentral

88.

Jane, E. P., Premkumar, D. R., Cavaleri, J. M., Sutera, P. A., Rajasekar, T., & Pollack, I. F. (2016). Dinaciclib, a cyclin-dependent kinase inhibitor promotes proteasomal degradation of Mcl-1 and enhances ABT-737-mediated cell death in malignant human glioma cell liness. The Journal of Pharmacology and Experimental Therapeutics, 356(2), 354–365. https://doi.org/10.1124/jpet.115.230052.CrossRefPubMedPubMedCentral

89.

Juric, V., & Murphy, B. (2020). Cyclin-dependent kinase inhibitors in brain cancer: Current state and future directions. Cancer Drug Resist. https://doi.org/10.20517/cdr.2019.105.

90.

Goel, S., Decristo, M. J., Watt, A. C., Brinjones, H., Sceneay, J., Li, B. B., et al. (2017). CDK4/6 inhibition triggers anti-tumour immunity. Nature, 548(7668), 471–475. https://doi.org/10.1038/nature23465.CrossRefPubMedPubMedCentral

91.

Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., et al. (2018). Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature, 553(7686), 91–95. https://doi.org/10.1038/nature25015.CrossRefPubMed

92.

Bonelli, M., La Monica, S., Fumarola, C., & Alfieri, R. (2019). Multiple effects of CDK4/6 inhibition in cancer: From cell cycle arrest to immunomodulation. Biochemical Pharmacology. Elsevier Inc, 170, 113676. https://doi.org/10.1016/j.bcp.2019.113676.CrossRefPubMed

93.

Schaer, D. A., Beckmann, R. P., Dempsey, J. A., Huber, L., Forest, A., Amaladas, N., et al. (2018). The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade. Cell Reports, 22(11), 2809–2817. https://doi.org/10.1016/j.celrep.2018.02.053.CrossRef

94.

Guo, T., Li, B., Gu, C., Chen, X., Han, M., Liu, X., & Xu, C. (2019). PGC-1α inhibits polyamine metabolism in Cyclin E1-driven ovarian cancer. Cancer Medicine, 8(18), 7754–7761. https://doi.org/10.1002/cam4.2637.CrossRefPubMedPubMedCentral

95.

Ke, C., Hou, H., Li, J., Su, K., Huang, C., Lin, Y., et al. (2020). Extracellular vesicle delivery of TRAIL eradicates resistant tumor growth in combination with CDK inhibition by dinaciclib. Cancers, 12(5), 1157. https://doi.org/10.3390/cancers12051157.CrossRefPubMedCentral

96.

Md Sakib Hossain, D., Javaid, S., Cai, M., Zhang, C., Sawant, A., Hinton, M., et al. (2018). Dinaciclib induces immunogenic cell death and enhances anti- PD1–mediated tumor suppression. Journal of Clinical Investigation, 128(2), 644–654. https://doi.org/10.1172/JCI94586.CrossRef

97.

Nagaraja, S., Vitanza, N. A., Woo, P. J., Taylor, K. R., Liu, F., Zhang, L., et al. (2017). Transcriptional dependencies in diffuse intrinsic pontine glioma. Cancer Cell, 31(5), 635–652.e6. https://doi.org/10.1016/j.ccell.2017.03.011.CrossRefPubMedPubMedCentral

98.

Wang, J., Zhang, R., Lin, Z., Zhang, S., Chen, Y., Tang, J., et al. (2020). CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38α/MYC/PD-L1 signaling in non-small cell lung cancer. Journal of Hematology & Oncology, 13(1). https://doi.org/10.1186/s13045-020-00926-x.

99.

Sorvina, A., Shandala, T., Wang, S., Sharkey, D. J., Parkinson-Lawrence, E., Selemidis, S., & Brooks, D. A. (2020). CDKI-73 is a novel pharmacological inhibitor of Rab11 cargo delivery and innate immune secretion. Cells, 9(2), 372. https://doi.org/10.3390/cells9020372.CrossRefPubMedCentral

100.

Zhang, H., Christensen, C. L., Dries, R., Oser, M. G., Deng, J., Diskin, B., et al. (2020). CDK7 inhibition potentiates genome instability triggering anti-tumor immunity in small cell lung cancer. Cancer Cell, 37(1), 37–54.e9. https://doi.org/10.1016/j.ccell.2019.11.003.CrossRefPubMed

101.

Chen, E. W., Tay, N. Q., Brzostek, J., Gascoigne, N. R. J., & Rybakin, V. (2019). A dual inhibitor of Cdc7/Cdk9 potently suppresses T cell activation. Frontiers in Immunology, 10, 1718. https://doi.org/10.3389/fimmu.2019.01718.CrossRefPubMedPubMedCentral

102.

Wang, K., Hampson, P., Hazeldine, J., Krystof, V., Strnad, M., Pechan, P., & Lord, J. M. (2012). Cyclin-dependent kinase 9 activity regulates neutrophil spontaneous apoptosis. PLoS One, 7(1). https://doi.org/10.1371/journal.pone.0030128.

103.

Erdő, F., Nagy, I., Tóth, B., Bui, A., Molnár, É., Tímár, Z., et al. (2017). Abcb1a (P-glycoprotein) limits brain exposure of the anticancer drug candidate seliciclib in vivo in adult mice. Brain Research Bulletin, 132, 232–236. https://doi.org/10.1016/j.brainresbull.2017.06.013.CrossRefPubMed

104.

Liao, X. M., Hong, Y., Mao, Y., Chen, N., Wang, Q., Wang, Z., et al. (2020). SPH3643: A novel cyclin-dependent kinase 4/6 inhibitor with good anticancer efficacy and strong blood-brain barrier permeability. Cancer Science, 111(5), 1761–1773. https://doi.org/10.1111/cas.14367.CrossRefPubMedPubMedCentral

105.

Zhang, X., Lv, H., Zhou, Q., Elkholi, R., Chipuk, J. E., Reddy, M. V. R., et al. (2014). Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Molecular Cancer Therapeutics, 13(5), 1105–1116. https://doi.org/10.1158/1535-7163.MCT-13-0847.CrossRefPubMedPubMedCentral

106.

De Gooijer, M. C., Zhang, P., Thota, N., Mayayo-Peralta, I., Buil, L. C. M., Beijnen, J. H., & Van Tellingen, O. (2015). P-glycoprotein and breast cancer resistance protein restrict the brain penetration of the CDK4/6 inhibitor palbociclib. Investigational New Drugs, 33(5), 1012–1019. https://doi.org/10.1007/s10637-015-0266-y.CrossRefPubMed

107.

Parrish, K. E., Pokorny, J., Mittapalli, R. K., Bakken, K., Sarkaria, J. N., & Elmquist, W. F. (2015). Efflux transporters at the blood-brain barrier limit delivery and efficacy of cyclin-dependent kinase 4/6 inhibitor palbociclib (PD-0332991) in an orthotopic brain tumor model. The Journal of Pharmacology and Experimental Therapeutics, 355(2), 264–271. https://doi.org/10.1124/jpet.115.228213.CrossRefPubMedPubMedCentral

108.

Asby, D. J., Killick-Cole, C. L., Boulter, L. J., Singleton, W. G. B., Asby, C. A., Wyatt, M. J., et al. (2018). Combined use of CDK4/6 and mTOR inhibitors induce synergistic growth arrest of diffuse intrinsic pontine glioma cells via mutual downregulation of mTORC1 activity. Cancer Management and Research, 10, 3483–3500. https://doi.org/10.2147/CMAR.S167095.CrossRefPubMedPubMedCentral

109.

Martínez-Chávez, A., Van Hoppe, S., Rosing, H., Lebre, M. C., Tibben, M., Beijnen, J. H., & Schinkel, A. H. (2019). P-glycoprotein limits ribociclib brain exposure and CYP3A4 restricts its oral bioavailability. Molecular Pharmaceutics, 16(9), 3842–3852. https://doi.org/10.1021/acs.molpharmaceut.9b00475.CrossRefPubMed

110.

Yin, L., Li, H., Liu, W., Yao, Z., Cheng, Z., Zhang, H., & Zou, H. (2018). A highly potent CDK4/6 inhibitor was rationally designed to overcome blood brain barrier in gliobastoma therapy. European Journal of Medicinal Chemistry, 144, 1–28. https://doi.org/10.1016/j.ejmech.2017.12.003.CrossRefPubMed

111.

Bronner, S. M., Merrick, K. A., Murray, J., Salphati, L., Moffat, J. G., Pang, J., et al. (2019). Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma. Bioorganic and Medicinal Chemistry Letters, 29(16), 2294–2301. https://doi.org/10.1016/j.bmcl.2019.06.021.CrossRefPubMed

112.

Lubanska, D., & Porter, L. (2017). Revisiting CDK inhibitors for treatment of glioblastoma multiforme. Drugs in R&D. Springer International Publishing. https://doi.org/10.1007/s40268-017-0180-1.

113.

Nebot-Bral, L., Brandao, D., Verlingue, L., Rouleau, E., Caron, O., Despras, E., et al. (2017). Hypermutated tumours in the era of immunotherapy: The paradigm of personalised medicine. European Journal of Cancer (Oxford, England : 1990), 84, 290–303. https://doi.org/10.1016/j.ejca.2017.07.026.CrossRef

114.

Galon, J., & Bruni, D. (2019). Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nature Reviews. Drug Discovery, 18(3), 197–218. https://doi.org/10.1038/s41573-018-0007-y.CrossRefPubMed

115.

Wang, H. f., Wang, S. s., Tang, Y. J., Chen, Y., Zheng, M., Tang, Y. l., & Liang, X. h. (2019). The double-edged sword—How human papillomaviruses interact with immunity in head and neck cancer. Frontiers in Immunology. Frontiers Media S.A. https://doi.org/10.3389/fimmu.2019.00653.

116.

Wuerdemann, N., Gültekin, S. E., Pütz, K., Wittekindt, C., Huebbers, C. U., Sharma, S. J., et al. (2020). PD-L1 expression and a high tumor infiltrate of CD8+ lymphocytes predict outcome in patients with oropharyngeal squamous cells carcinoma. International Journal of Molecular Sciences, 21(15), 1–17. https://doi.org/10.3390/ijms21155228.CrossRef

117.

Luoto, S., Hermelo, I., Vuorinen, E. M., Hannus, P., Kesseli, J., Nykter, M., & Granberg, K. J. (2018). Computational characterization of suppressive immune microenvironments in glioblastoma. Cancer Research, 78(19), 5574–5585. https://doi.org/10.1158/0008-5472.CAN-17-3714.CrossRefPubMed

118.

Grabowski, M. M., Sankey, E. W., Ryan, K. J., Chongsathidkiet, P., Lorrey, S. J., Wilkinson, D. S., & Fecci, P. E. (2020). Immune suppression in gliomas. Journal of Neuro-Oncology. https://doi.org/10.1007/s11060-020-03483-y.

119.

Zhang, H., Zhou, Y., Cui, B., Liu, Z., & Shen, H. (2020, June 1). Novel insights into astrocyte-mediated signaling of proliferation, invasion and tumor immune microenvironment in glioblastoma. Biomedicine & Pharmacotherapy. Elsevier Masson SAS. https://doi.org/10.1016/j.biopha.2020.110086.

120.

Petroni, G., Formenti, S. C., Chen-Kiang, S., & Galluzzi, L. (2020). Immunomodulation by anticancer cell cycle inhibitors. Nature Reviews. Immunology, 1–11. https://doi.org/10.1038/s41577-020-0300-y.

121.

Vijayaraghavan, S., Karakas, C., Doostan, I., Chen, X., Bui, T., Yi, M., et al. (2017). CDK4/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin e negative cancers. Nature Communications, 8. https://doi.org/10.1038/ncomms15916.

122.

Knudsen, E. S., Pruitt, S. C., Hershberger, P. A., Witkiewicz, A. K., & Goodrich, D. W. (2019, May 1). Cell cycle and beyond: Exploiting new RB1 controlled mechanisms for cancer therapy. Trends in Cancer. Cell Press. https://doi.org/10.1016/j.trecan.2019.03.005.

123.

Dowless, M., Lowery, C. D., Shackleford, T., Renschler, M., Stephens, J., Flack, R., et al. (2018). Abemaciclib is active in preclinical models of Ewing sarcoma via multipronged regulation of cell cycle, DNA methylation, and interferon pathway signaling. Clinical Cancer Research, 24(23), 6028–6039. https://doi.org/10.1158/1078-0432.CCR-18-1256.CrossRefPubMedPubMedCentral

124.

Appleman, L. J., Berezovskaya, A., Grass, I., & Boussiotis, V. A. (2000). CD28 costimulation mediates T cell expansion via IL-2-independent and IL-2-dependent regulation of cell cycle progression. Journal of Immunology, 164(1), 144–151. https://doi.org/10.4049/jimmunol.164.1.144.CrossRef

125.

Hurvitz, S. A., Martin, M., Press, M. F., Chan, D., Fernandez-Abad, M., Petru, E., et al. (2020). Potent cell-cycle inhibition and upregulation of immune response with abemaciclib and anastrozole in Neomonarch, phase II neoadjuvant study in HR+/HER2- breast cancer. Clinical Cancer Research, 26(3), 566–580. https://doi.org/10.1158/1078-0432.CCR-19-1425.CrossRefPubMed

126.

Oh, S. J., Cho, H., Kim, S., Noh, K. H., Song, K. H., Lee, H. J., et al. (2018). Targeting cyclin D-CDK4/6 sensitizes immune-refractory cancer by blocking the SCP3–NANOG axis. Cancer Research, 78(10), 2638–2653. https://doi.org/10.1158/0008-5472.CAN-17-2325.CrossRefPubMed

127.

Guan, X., LaPak, K. M., Hennessey, R. C., Yu, C. Y., Shakya, R., Zhang, J., & Burd, C. E. (2017). Stromal senescence by prolonged CDK4/6 inhibition potentiates tumor growth. Molecular Cancer Research, 15(3), 237–249. https://doi.org/10.1158/1541-7786.MCR-16-0319.CrossRefPubMed

128.

Di Mitri, D., Toso, A., Chen, J. J., Sarti, M., Pinton, S., Jost, T. R., et al. (2014). Tumour-infiltrating Gr-1 + myeloid cells antagonize senescence in cancer. Nature, 515(7525), 134–137. https://doi.org/10.1038/nature13638.CrossRefPubMed

129.

Kietzman, W. B., Graham, G. T., Ory, V., Sharif, G. M., Kushner, M. H., Gallanis, G. T., et al. (2019). Short- and long-term effects of CDK4/6 inhibition on early-stage breast cancer. Molecular Cancer Therapeutics, 18(12), 2220–2232. https://doi.org/10.1158/1535-7163.MCT-19-0231.CrossRefPubMedPubMedCentral

130.

Zhang, P., Miska, J., Lee-Chang, C., Rashidi, A., Panek, W. K., An, S., et al. (2019). Therapeutic targeting of tumor-associated myeloid cells synergizes with radiation therapy for glioblastoma. Proceedings of the National Academy of Sciences of the United States of America, 116(47), 23714–23723. https://doi.org/10.1073/pnas.1906346116.CrossRefPubMedPubMedCentral

131.

Zhang, H., Pandey, S., Travers, M., Sun, H., Morton, G., Madzo, J., et al. (2018). Targeting CDK9 reactivates epigenetically silenced genes in cancer. Cell, 175(5), 1244–1258.e26. https://doi.org/10.1016/j.cell.2018.09.051.CrossRefPubMedPubMedCentral

132.

Jin, X., Ding, D., Yan, Y., Li, H., Wang, B., Ma, L., et al. (2019). Phosphorylated RB promotes cancer immunity by inhibiting NF-κB activation and PD-L1 expression. Molecular Cell, 73(1), 22–35.e6. https://doi.org/10.1016/j.molcel.2018.10.034.CrossRefPubMed

133.

Connecting the Dots: Therapy-Induced Senescence and a Tumor-Suppressive Immune Microenvironment. - PubMed - NCBI. (n.d.). Retrieved May 4, 2020, from https://www.ncbi.nlm.nih.gov/pubmed/?term=vilgelm+connecting+the+dots.

134.

Yu, J., Yan, J., Guo, Q., Chi, Z., Tang, B., Zheng, B., et al. (2019). Genetic aberrations in the CDK4 pathway are associated with innate resistance to PD-1 blockade in Chinese patients with non-cutaneous melanoma. Clinical Cancer Research, 25(21), 6511–6523. https://doi.org/10.1158/1078-0432.CCR-19-0475.CrossRefPubMed

135.

Teo, Z. L., Versaci, S., Dushyanthen, S., Caramia, F., Savas, P., Mintoff, C. P., et al. (2017). Combined CDK4/6 and PI3Kα inhibition is synergistic and immunogenic in triple-negative breast cancer. Cancer Research, 77(22), 6340–6352. https://doi.org/10.1158/0008-5472.CAN-17-2210.CrossRefPubMed

136.

Goymer, P. (2008). Natural selection: The evolution of cancer. Nature. Nature Publishing Group, 454, 1046–1048. https://doi.org/10.1038/4541046a.CrossRefPubMed

137.

Kettner, N. M., Vijayaraghavan, S., Durak, M. G., Bui, T., Kohansal, M., Ha, M. J., et al. (2019). Combined inhibition of STAT3 and DNA repair in palbociclib-resistant er-positive breast cancer. Clinical Cancer Research, 25(13), 3996–4013. https://doi.org/10.1158/1078-0432.CCR-18-3274.CrossRefPubMedPubMedCentral

138.

Wang, Q., Guldner, I. H., Golomb, S. M., Sun, L., Harris, J. A., Lu, X., & Zhang, S. (2019). Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor-resistant HER2-positive breast cancer. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-11729-1.

139.

Knudsen, E. S., & Witkiewicz, A. K. (2017). The strange case of CDK4/6 inhibitors: mechanisms, resistance, and combination strategies. Trends in Cancer. Cell Press. https://doi.org/10.1016/j.trecan.2016.11.006.

140.

Iida, M., Toyosawa, D., Nakamura, M., Tsuboi, K., Tokuda, E., Niwa, T., Ishida, T., & Hayashi, S. I. (2020). Decreased ER dependency after acquired resistance to CDK4/6 inhibitors. Breast Cancer, 27, 963–972. https://doi.org/10.1007/s12282-020-01090-3.CrossRefPubMed

141.

Liu, J., Lee, W., Jiang, Z., Chen, Z., Jhunjhunwala, S., Haverty, P. M., et al. (2012). Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Genome Research, 22(12), 2315–2327. https://doi.org/10.1101/gr.140988.112.CrossRefPubMedPubMedCentral

142.

Wong, C. H., Ma, B. B. Y., Hui, C. W. C., Lo, K. W., Hui, E. P., & Chan, A. T. C. (2018). Preclinical evaluation of ribociclib and its synergistic effect in combination with alpelisib in non-keratinizing nasopharyngeal carcinoma. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-26201-1.

143.

Olmez, I., Zhang, Y., Manigat, L., Benamar, M., Brenneman, B., Nakano, I., et al. (2018). Combined c-Met/Trk inhibition overcomes resistance to CDK4/6 inhibitors in Glioblastoma. Cancer Research, 78(15), 4360–4369. https://doi.org/10.1158/0008-5472.CAN-17-3124.CrossRefPubMedPubMedCentral

144.

Michaloglou, C., Crafter, C., Siersbaek, R., Delpuech, O., Curwen, J. O., Carnevalli, L. S., et al. (2018). Combined inhibition of mtor and cdk4/6 is required for optimal blockade of e2f function and long-term growth inhibition in estrogen receptor–positive breast cancer. Molecular Cancer Therapeutics, 17(5), 908–920. https://doi.org/10.1158/1535-7163.MCT-17-0537.CrossRefPubMedPubMedCentral

145.

Romano, G., Chen, P. L., Song, P., McQuade, J. L., Liang, R. J., Liu, M., et al. (2018). A preexisting rare PIK3CA e545k subpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling. Cancer Discovery, 8(5), 556–567. https://doi.org/10.1158/2159-8290.CD-17-0745.CrossRefPubMedPubMedCentral

146.

Wu, J., Liang, Y., Tan, Y., Tang, Y., Song, H., Wang, Z., et al. (2020). CDK9 inhibitors reactivate p53 by downregulating iASPP. Cellular Signalling, 67. https://doi.org/10.1016/j.cellsig.2019.109508.

147.

Fernández-Aroca, D. M., Roche, O., Sabater, S., Pascual-Serra, R., Ortega-Muelas, M., Sánchez Pérez, I., et al. (2019). P53 pathway is a major determinant in the radiosensitizing effect of Palbociclib: Implication in cancer therapy. Cancer Letters, 451, 23–33. https://doi.org/10.1016/j.canlet.2019.02.049.CrossRefPubMed

148.

Naz, S., Sowers, A., Choudhuri, R., Wissler, M., Gamson, J., Mathias, A., et al. (2018). Abemaciclib, a selective CDK4/6 inhibitor, enhances the radiosensitivity of non–small cell lung cancer in vitro and in vivo. Clinical Cancer Research, 24(16), 3994–4005. https://doi.org/10.1158/1078-0432.CCR-17-3575.CrossRefPubMedPubMedCentral

149.

Liu, S., Yuan, D., Li, Y., Qi, Q., Guo, B., Yang, S., et al. (2019). Involvement of phosphatase and tensin homolog in cyclin-dependent kinase 4/6 inhibitor-induced blockade of glioblastoma. Frontiers in Pharmacology, 10. https://doi.org/10.3389/fphar.2019.01316.

Title: Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma—backbone or add-on in immune-oncology?
Authors: Christin Riess
Nina Irmscher
Inken Salewski
Daniel Strüder
Carl-Friedrich Classen
Christina Große-Thie
Christian Junghanss
Claudia Maletzki
Publication date: 01-03-2021
Publisher: Springer US
Keywords: Glioblastoma
Glioblastoma
Glioblastoma
Biomarkers
Published in: Cancer and Metastasis Reviews / Issue 1/2021
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-020-09940-4

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