1,855
Views
1
CrossRef citations to date
0
Altmetric
Research Paper

Synthetic lethality of cyclin-dependent kinase inhibitor Dinaciclib with VHL-deficiency allows for selective targeting of clear cell renal cell carcinoma

, , , , , , , & show all
Pages 1103-1119 | Received 30 Nov 2021, Accepted 08 Feb 2022, Published online: 04 Mar 2022

References

  • Cancer Stat Facts: cancer of the Kidney and Renal Pelvis Cancer National Institute of Health: National Cancer Institute; [cited 2021]. Available from: https://seer.cancer.gov/statfacts/html/kidrp.html
  • Shen C, Kaelin WG Jr. The VHL/HIF axis in clear cell renal carcinoma. Semin Cancer Biol. 2013 Feb;23(1):18–25.
  • Geynisman DM, Maranchie JK, Ball MW, et al. A 25 year perspective on the evolution and advances in an understanding of the biology, evaluation and treatment of kidney cancer. Urol Oncol. 2021 Jun 4;39:548–560.
  • Asghar U, Witkiewicz AK, Turner NC, et al. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov. 2015 Jan 30;14:130.
  • Chou J, Quigley DA, Robinson TM, et al. Transcription-Associated cyclin-dependent kinases as targets and biomarkers for cancer therapy. Cancer Discov. 2020 Mar;10(3):351–370.
  • Zhang M, Zhang L, Hei R, et al. CDK inhibitors in cancer therapy, an overview of recent development. Am J Cancer Res. 2021;11(5):1913–1935.
  • Stadler WM, Vogelzang NJ, Amato R, et al. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: a University of Chicago Phase II Consortium study. J Clin Oncol. 2000 Jan;18(2):371–375.
  • Van Veldhuizen PJ, Faulkner JR, Lara PN Jr., et al. A phase II study of flavopiridol in patients with advanced renal cell carcinoma: results of Southwest Oncology Group Trial 0109. Cancer Chemother Pharmacol. 2005 Jul;56(1):39–45.
  • Chen D, Sun X, Zhang X, et al. Inhibition of the CDK4/6-Cyclin D-Rb pathway by ribociclib augments chemotherapy and immunotherapy in renal cell carcinoma. Biomed Res Int. 2020;2020:9525207.
  • Nicholson HE, Tariq Z, Housden BE, et al. HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species. Sci Signal. 2019 Oct 1;12(601). DOI:https://doi.org/10.1126/scisignal.aay0482.
  • Bommi-Reddy A, Almeciga I, Sawyer J, et al. Kinase requirements in human cells: III. Altered kinase requirements in VHL-/- cancer cells detected in a pilot synthetic lethal screen. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16484–16489.
  • Xiao H, Zeng J, Li H, et al. MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis. Oncotarget. 2015 May 30;6(15):13201–13215.
  • Atkins DJ, Gingert C, Justenhoven C, et al. Concomitant deregulation of HIF1alpha and cell cycle proteins in VHL-mutated renal cell carcinomas. Virchows Arch. 2005 Sep;447(3):634–642.
  • Hongo F, Takaha N, Oishi M, et al. CDK1 and CDK2 activity is a strong predictor of renal cell carcinoma recurrence. Urol Oncol. 2014 Nov;32(8):1240–1246.
  • Li Y, Quan J, Chen F, et al. MiR-31-5p acts as a tumor suppressor in renal cell carcinoma by targeting cyclin-dependent kinase 1 (CDK1). Biomed Pharmacother. 2019 Mar 1;111:517–526.
  • Wang X, Chen X, Han W, et al. miR-200c targets CDK2 and suppresses tumorigenesis in renal cell carcinoma. Mol Cancer Res. 2015 Dec;13(12):1567–1577.
  • Xiao H, Xiao W, Cao J, et al. miR-206 functions as a novel cell cycle regulator and tumor suppressor in clear-cell renal cell carcinoma. Cancer Lett. 2016 Apr 28;374(1):107–116.
  • Goga A, Yang D, Tward AD, et al. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat Med. 2007 Jul;13(7):820–827.
  • Horiuchi D, Kusdra L, Huskey NE, et al. MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition. J Exp Med. 2012 April 9;209(4):679–696.
  • Gregory GP, Hogg SJ, Kats LM, et al. CDK9 inhibition by dinaciclib potently suppresses Mcl-1 to induce durable apoptotic responses in aggressive MYC-driven B-cell lymphoma in vivo. Leukemia. 2015 Jun;29(6):1437–1441.
  • Hashiguchi T, Bruss N, Best S, et al. Cyclin-Dependent Kinase-9 Is a therapeutic target in MYC-Expressing diffuse large B-Cell lymphoma. Mol Cancer Ther. 2019 Sep;18(9):1520–1532.
  • Huang C-H, Lujambio A, Zuber J, et al. CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma. Genes Dev. 2014 Aug 15;28(16):1800–1814.
  • Beroukhim R, Brunet J-P, Napoli AD, et al. Patterns of gene expression and copy-number alterations in von-Hippel Lindau Disease-Associated and sporadic clear cell carcinoma of the kidney. Cancer Res. 2009 Jun 1;69(11):4674–4681.
  • Sato Y, Yoshizato T, Shiraishi Y, et al. Integrated molecular analysis of clear-cell renal cell carcinoma. Nat Genet. 2013 Aug;45(8):860–867.
  • Gordan JD, Bertovrt JA, Hu C-J, et al. HIF-2α promotes hypoxic cell proliferation by enhancing c-Myc transcriptional activity. Cancer Cell. 2007 April;11(4):335–347.
  • Gordan JD, Lal P, Dondeti VR, et al. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell. 2008 Dec 9;14(6):435–446.
  • Parry D, Guzi T, Shanahan F, et al. Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug 1;9(8):2344–2353.
  • Chen P, Lee NV, Hu W, et al. Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance. Mol Cancer Ther. 2016 Oct;15(10):2273–2281.
  • Johnson SF, Cruz C, Greifenberg AK, et al. CDK12 inhibition reverses De Novo and acquired PARP inhibitor resistance in BRCA wild-type and mutated models of triple-negative breast cancer. Cell Rep. 2016 Nov 22;17(9):2367–2381.
  • Alagpulinsa DA, Ayyadevara S, Yaccoby S, et al. A cyclin-dependent kinase inhibitor, dinaciclib, impairs homologous recombination and sensitizes multiple myeloma cells to PARP inhibition. Mol Cancer Ther. 2016 Feb;15(2):241–250.
  • Baker A, Gregory GP, Verbrugge I, et al. The CDK9 inhibitor dinaciclib exerts potent apoptotic and antitumor effects in preclinical models of MLL-Rearranged acute myeloid leukemia. Cancer Res. 2016 Mar 1;76(5):1158–1169.
  • Chen -X-X, Xie -F-F, Zhu X-J, et al. Cyclin-dependent kinase inhibitor dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer. Oncotarget. 2015 Mar 30;6(17):14926–14939.
  • Hossain DMS, Javaid S, Cai M, et al. Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor suppression. J Clin Invest. 2018 Feb 1;128(2):644–654.
  • Hu C, Dadon T, Chenna V, et al. Combined inhibition of cyclin-dependent kinases (Dinaciclib) and AKT (MK-2206) blocks pancreatic tumor growth and metastases in patient-derived xenograft models. Mol Cancer Ther. 2015 Jul;14(7):1532–1539.
  • Mita MM, Joy AA, Mita A, et al. Randomized Phase II trial of the cyclin-dependent kinase inhibitor Dinaciclib (MK-7965) versus capecitabine in patients with advanced breast cancer. Clin Breast Cancer. 2014 Jun 1;14(3):169–176.
  • Stephenson JJ, Nemunaitis J, Joy AA, et al. Randomized phase 2 study of the cyclin-dependent kinase inhibitor dinaciclib (MK-7965) versus erlotinib in patients with non-small cell lung cancer. Lung Cancer. 2014 Feb 1;83(2):219–223.
  • Kumar SK, LaPlant B, Chng WJ, et al. Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015 Jan 15;125(3):443–448.
  • Gojo I, Walker A, Cooper M, et al. Phase II study of the cyclin-dependent kinase (CDK) inhibitor Dinaciclib (SCH 727965) in patients with advanced acute leukemias. Blood. 2010 Nov 19;116(21): 3287–3287.
  • Diehn M, Cho RW, Clarke MF. Therapeutic implications of the cancer stem cell hypothesis. Semin Radiat Oncol. 2009 Apr;19(2):78–86.
  • Peired AJ, Sisti A, Romagnani P. Renal cancer stem cells: characterization and targeted therapies. Stem Cells Int. 2016;2016:1–12.
  • Hu J, Guan W, Liu P, et al. Endoglin is essential for the maintenance of self-renewal and chemoresistance in renal cancer stem cells. Stem Cell Reports. 2017 Aug 8;9(2):464–477.
  • Hu J, Guan W, Yan L, et al. Cancer stem cell marker Endoglin (CD105) induces epithelial mesenchymal transition (EMT) but not metastasis in clear cell renal cell carcinoma. Stem Cells Int. 2019;2019:9060152.
  • Bussolati B, Bruno S, Grange C, et al. Identification of a tumor-initiating stem cell population in human renal carcinomas. FASEB J. 2008 July 9;22(10):3696–3705.
  • Nelson LJ, Wright HJ, Dinh NB, et al. Src kinase is biphosphorylated at Y416/Y527 and activates the CUB-Domain containing protein 1/protein kinase c delta pathway in a subset of triple-negative breast cancers. Am J Pathol. 2020 Feb;190(2):484–502.
  • Razorenova OV, Ivanov AV, Budanov AV, et al. Virus-based reporter systems for monitoring transcriptional activity of hypoxia-inducible factor 1. Gene. 2005 Apr 25;350(1):89–98.
  • Wright HJ, Hou J, Xu B, et al. CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation. Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):E6556–E6565.
  • Thompson JM, Alvarez A, Singha MK, et al. Targeting the mevalonate pathway suppresses VHL-Deficient CC-RCC through an HIF-Dependent mechanism. Mol Cancer Ther. 2018 Aug;17(8):1781–1792.
  • Bragelmann J, Dammert MA, Dietlein F, et al. Systematic kinase inhibitor profiling identifies CDK9 as a synthetic lethal target in NUT midline carcinoma. Cell Rep. 2017 Sep 19;20(12):2833–2845.
  • Tse C, Shoemaker AR, Adickes J, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008 May 1;68(9):3421–3428.
  • Howard D, James D, and Murphy K, et al. Dinaciclib, a bimodal agent effective against endometrial cancer. Cancers (Basel). 2021 Mar 6;13(5):1135.
  • Mita MM, Mita AC, Moseley JL, et al. Phase 1 safety, pharmacokinetic and pharmacodynamic study of the cyclin-dependent kinase inhibitor dinaciclib administered every three weeks in patients with advanced malignancies. Br J Cancer. 2017 Oct 24;117(9):1258–1268.
  • Shroff EH, Eberlin LS, Dang VM, et al. MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6539–6544.
  • Bailey ST, Smith AM, Kardos J, et al. MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma. Nat Commun. 2017 Jun 8;8:15770.
  • Juengel E, Nowaz S, Makarevi J, et al. HDAC-inhibition counteracts everolimus resistance in renal cell carcinoma in vitro by diminishing cdk2 and cyclin A. Mol Cancer. 2014 Jun 16;13(1):152.
  • Tadesse S, Caldon EC, Tilley W, et al. Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: an Update. J Med Chem. 2019 May 9;62(9):4233–4251.
  • Poon E, Liang T, Jamin Y, et al. Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma. J Clin Invest. 2020 Nov 2;130(11):5875–5892.
  • Lai Y, Zeng T, Liang X, et al. Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy. Cancer Cell Int. 2019;19:221.
  • Razorenova OV, Castellini L, Colavitti R, et al. The apoptosis repressor with a CARD domain (ARC) gene is a direct hypoxia-inducible factor 1 target gene and promotes survival and proliferation of VHL-deficient renal cancer cells. Mol Cell Biol. 2014 Feb;34(4):739–751.
  • Li L, Pongtornpipat P, Tiutan T, et al. Synergistic induction of apoptosis in high-risk DLBCL by BCL2 inhibition with ABT-199 combined with pharmacologic loss of MCL1. Leukemia. 2015 Aug;29(8):1702–1712.
  • Glaser SP, Lee EF, Trounson E, et al. Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes Dev. 2012 Jan 15;26(2):120–125.
  • Yasuda Y, Ozasa H, Kim YH, et al. MCL1 inhibition is effective against a subset of small-cell lung cancer with high MCL1 and low BCL-XL expression. Cell Death Dis. 2020 Mar 9;11(3):177.
  • Derenne S, Monia B, Dean NM, et al. Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood. 2002 Jul 1;100(1):194–199.
  • Zhang B, Gojo I, Fenton RG. Myeloid cell factor-1 is a critical survival factor for multiple myeloma. Blood. 2002 Mar 15;99(6):1885–1893.
  • Bolomsky A, Vogler M, Kose MC, et al. MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents. J Hematol Oncol. 2020 Dec 11;13(1):173.
  • Paliouras AR, Buzzetti M, Shi L, et al. Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition. EMBO Mol Med. 2020 Jul 7;12(7):e11099.
  • Tsukahara T, Tanno Y, Watanabe Y. Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation. Nature. 2010 Oct 7;467(7316):719–723.
  • Yang L, Zhou F, Zhuang Y, et al. Acetyl-bufalin shows potent efficacy against non-small-cell lung cancer by targeting the CDK9/STAT3 signalling pathway. Br J Cancer. 2021 Feb;124(3):645–657.
  • Bretones G, Delgado MD, Leon J. Myc and cell cycle control. Biochim Biophys Acta. 2015 May;1849(5):506–516.
  • Gossage L, Eisen T, Maher ER. VHL, the story of a tumour suppressor gene. Nat Rev Cancer. 2015 Jan;15(1):55–64.
  • Tang B, Sun R, and Wang D, et al. ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor-activated cancer. Proc Natl Acad Sci U S A. 2021 Feb 23;118(8):e2019052118.
  • Zhao S, El-Deiry WS. Identification of Smurf2 as a HIF-1alpha degrading E3 ubiquitin ligase. Oncotarget. 2021 Sep 28;12(20):1970–1979.
  • Tabaro F, Minervini G, Sundus F, et al. VHLdb: a database of von Hippel-Lindau protein interactors and mutations. Sci Rep. 2016 Aug 11;6:31128.