Stromal senescence by prolonged CDK4/6 inhibition potentiates tumor growth

Molecular Cancer Research

Volumn 15, Issue 3, 2017, Pages 237-249

  Guan, Xiangnan ^a   LaPak, Kyle M ^a   Hennessey, Rebecca C ^a   Yu, Christina Y ^a   Shakya, Reena ^b   Zhang, Jianying ^a   Burd, Christin E ^a,b  

^a OHIO STATE UNIVERSITY   (United States)

^b OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PALBOCICLIB; PROTEIN MDM2; ANTINEOPLASTIC AGENT; PIPERAZINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE;

ANIMAL CELL; ARTICLE; CANCER CELL CULTURE; CANCER GROWTH; CELL AGING; CELL GROWTH; CELL PROLIFERATION; CONTROLLED STUDY; DNA DAMAGE; DOWN REGULATION; FIBROBLAST; FIBROBLAST CULTURE; GENOTYPE; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IN VIVO STUDY; MELANOMA CELL LINE; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; STROMA CELL; VALIDATION STUDY; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; DRUG EFFECTS; ENZYMOLOGY; HUMAN; MELANOMA, EXPERIMENTAL; PATHOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE; TUMOR MICROENVIRONMENT;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL AGING; CELL LINE, TUMOR; CYCLIN-DEPENDENT KINASE 4; CYCLIN-DEPENDENT KINASE 6; HUMANS; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED C57BL; PIPERAZINES; PROTEIN KINASE INHIBITORS; PYRIDINES; SIGNAL TRANSDUCTION; STROMAL CELLS; TUMOR MICROENVIRONMENT;

EID: 85015969441     PISSN: 15417786     EISSN: 15573125     Source Type: Journal    
DOI: 10.1158/1541-7786.MCR-16-0319     Document Type: Article

References (49)

1. Sharpless NE, Sherr CJ. Forging a signature of in vivo senescence. Nat Rev Cancer 2015;15:397-408.
2. Coppe J-P, Desprez P-Y, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 2010;5:99.
3. Campisi J, di Fagagna FdA. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 2007;8:729-40.
4. Burd CE, Sorrentino JA, Clark KS, Darr DB, Krishnamurthy J, Deal AM, et al. Monitoring tumorigenesis and senescence in vivo with a p16 INK4a-luciferase model. Cell 2013;152:340-51.
5. Witkiewicz AK, Knudsen KE, Dicker AP, Knudsen ES. The meaning of p16ink4a expression in tumors: functional significance, clinical associations and future developments. Cell Cycle 2011;10:2497-503.
6. Lugo R, Gabasa M, Francesca A, Puig M, Facchinetti F, Ramirez J, et al. Cancer cell-stromal cell crosstalk drives fibroblast senescence and tumor progression in large cell carcinoma of the lung in culture and in vivo [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20, 2016; New Orleans, LA. Philadelphia (PA): AACR; 2016.
7. Witkiewicz AK, Rivadeneira DB, Ertel A, Kline J, Hyslop T, Schwartz GF, et al. Association of RB/p16-pathway perturbations with DCIS recurrence: dependence on tumor versus tissue microenvironment. Am J Pathol 2011;179:1171-8.
8. Coppe J-P, Patil CK, Rodier F, Krtolica A, Beausejour CM, Parrinello S, et al. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS One 2010;5:e9188.
9. Coppe J-P, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008;6:2853-68.
10. Liu D, Hornsby PJ. Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Res 2007;67:3117-26.
11. Coppe J-P, Kauser K, Campisi J, Beausejour CM. Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence. J Biol Chem 2006;281:29568-74.
12. Ruhland MK, Loza AJ, Capietto AH, Luo X, Knolhoff BL, Flanagan KC, et al. Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. Nat Commun 2016;7:11762.
13. Antonia SJ, Larkin J, Ascierto PA. Immuno-oncology combinations: a review of clinical experience and future prospects. Clin Cancer Res 2014; 20:6258-68.
14. Sosman J. MEK+ CDK4 a regimen for non-BRAFV6000 melanoma. JTransl Med2015;13:K9.
15. Diab A, Martin A, Simpson L, Algazi AP, Chawla P, Kim DW, et al. Phase I trial of the CDK 4/6 inhibitor, P1446A-05 (voruciclib) in combination with the BRAF inhibitor (BRAFi), vemurafenib in advanced, BRAF-mutant melanoma. J Clin Oncol 33, 2015 (suppl; abstr 9076).
16. Sosman JA, Kittaneh M, Lolkema MP, Postow MA, Schwartz G, Franklin C, et al. A phase 1b/2 study of LEE011 in combination with binimetinib (MEK162) in patients with NRAS-mutant melanoma: early encouraging clinical activity. J Clin Oncol 32:5s, 2014 (suppl; abstr 9009).
17. Capparelli C, Chiavarina B, Whitaker-Menezes D, Pestell TG, Pestell RG, Hulit J, et al. CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, "fueling" tumor growth via paracrine interactions, without an increase in neo-angiogenesis. Cell Cycle 2012;11:3599-610.
18. Burd CE, Liu W, Huynh MV, Waqas MA, Gillahan JE, Clark KS, et al. Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma. Cancer Discov 2014;4:1418-29.
19. Monahan K, Rozenberg G, Krishnamurthy J, Johnson S, Liu W, Bradford M, et al. Somatic p16INK4a loss accelerates melanomagenesis. Oncogene 2010;29:5809-17.
20. Dhomen N, Reis-Filho JS, da Rocha Dias S, Hayward R, Savage K, Delmas V, et al. Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell 2009;15:294-303.
21. Wang J, Jacob NK, Ladner KJ, Beg A, Perko JD, Tanner SM, et al. RelA/p65 functions to maintain cellular senescence by regulating genomic stability and DNA repair. EMBO Rep 2009;10:1272-8.
22. di Adda di Fagagna F. Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer 2008;8:512-22.
23. Kovatcheva M, Liu DD, Dickson MA, Klein ME, O'Connor R, Wilder FO, et al. MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition. Oncotarget 2015;6:8226.
24. Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, Bolden JE, et al. Control of the senescence-associated secretory phenotype by NF/cB promotes senescence and enhances chemosensitivity. Genes Dev 2011; 25:2125-36.
25. Freund A, Patil CK, Campisi J. p38MAPK is a novel DNA damage respon-seindependent regulator of the senescenceassociated secretory phenotype. EMBO J 2011;30:1536-48.
26. Dilley TK, Bowden GT, Chen QM. Novel mechanisms of sublethal oxidant toxicity: induction of premature senescence in human fibroblasts confers tumor promoter activity. Exp Cell Res 2003;290:38-48.
27. Krtolica A, Parrinello S, Lockett S, Desprez P-Y, Campisi J. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci USA 2001;98:12072-7.
28. Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 2013;15:978-90.
29. Parrinello S, Coppe J-P, Krtolica A, Campisi J. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J Cell Sci 2005;118:485-96.
30. Pazolli E, Luo X, Brehm S, Carbery K, Chung J-J, Prior JL, et al. Senescent stromal-derived osteopontin promotes preneoplastic cell growth. Cancer Res 2009;69:1230-9.
31. Freund A, Orjalo AV, Desprez P-Y, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med 2010;16:238-46.
32. Shan W, Yang G, Liu J. The inflammatory network: bridging senescent stroma and epithelial tumorigenesis. Front Biosci 2009;14:4044.
33. Coppe J-P, Rodier F, Patil CK, Freund A, Desprez P-Y, Campisi J. Tumor suppressor and aging biomarker p16INK4a induces cellular senescence without the associated inflammatory secretory phenotype. J Biol Chem 2011;286:36396-403.
34. Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science 2015;349:aaa5612.
35. Herranz N, Gallage S, Mellone M, Wuestefeld T, Klotz S, Hanley CJ, et al. mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nat Cell Biol 2015;17:1205-17.
36. Malaquin N, Martinez A, Rodier F. Keeping the senescence secretome under control: molecular reins on the senescence-associated secretory phenotype. Exp Gerontol 2016;82:39-49.
37. Zhang Z, Wang H, Li M, Agrawal S, Chen X, Zhang R. MDM2 is a negative regulator of p21WAF1/CIP1, independent of p53. J Biol Chem 2004;279: 16000-6.
38. Oswald E, Santo VE, Rudisch A, Brito C, Sommergruber W, Dolznig H, et al. Co-injection of human fibroblasts significantly enhances tumorigenicity of orthotopically implanted human non-small cell lung cancer cells in immunocompromised mice [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016; New Orleans, LA. Philadelphia (PA): AACR; 2016.
39. Di Mitri D, Toso A, Chen JJ, Sarti M, Pinton S, Jost TR, et al. Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer. Nature 2014;515:134-7.
40. O'Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol 2016;13:417-30.
41. Schwartz GK, LoRusso PM, Dickson MA, Randolph SS, Shaik MN, Wilner KD, et al. Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1). Br J Cancer 2011;104:1862-8.
42. Flaherty KT, LoRusso PM, DeMichele A, Abramson VG, Courtney R, Randolph SS, et al. Phase I, dose-escalation trial of the oral cyclin-depen-dent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer. Clin Cancer Res 2012;18: 568-76.
43. Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther 2004; 3:1427-38.
44. Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, et al. 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 Discov 2016;6:740-53.
45. Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov 2015;14:130-46.
46. Shapiro G, Rosen LS, Tolcher AW, Goldman JW, Gandhi L, Papadopoulos KP, et al. A first-in-human phase I study of the CDK4/6 inhibitor, LY2835219, for patients with advanced cancer. J Clin Oncol 31, 2013 (suppl; abstr 2500).
47. Infante JR, Shapiro G, Witteveen P, Gerecitano JF, Ribrag V, Chugh R, et al. A phase I study of the single-agent CDK4/6 inhibitor LEE011 in pts with advanced solid tumors and lymphomas. J Clin Oncol 32:5s, 2014 (suppl; abstr 2528).
48. Van Herpen C, Postow M, Carlino M, Kalkavan H, Weise A, Amaria R, et al. 3300 A phase 1b/2 study of ribociclib (LEE011; CDK4/6 inhibitor) in combination with binimetinib (MEK162; MEK inhibitor) in patients with NRAS-mutant melanoma. Eur J Cancer 2015;51:S663.
49. Taylor M, Sosman J, Gonzalez R, Carlino M, Kittaneh M, Lolkema M, et al. 1086oPhase Ib/II study of LEE011 (CDK4/6 inhibitor) and LGX818 (BRAF inhibitor) in BRAF-mutant melanoma. Ann Oncol 2014;25:iv374-iv5.