340
Views
15
CrossRef citations to date
0
Altmetric
Review

Emerging oral VEGF inhibitors for the treatment of renal cell carcinoma

, & ORCID Icon
Pages 121-130 | Received 27 Jul 2018, Accepted 11 Dec 2018, Published online: 21 Dec 2018

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7–30. PubMed PMID: 29313949.
  • Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol. 2016 Jul;70(1):93–105. PubMed PMID: 26935559.
  • Udager AM, Mehra R. Morphologic, molecular, and taxonomic evolution of renal cell carcinoma: a conceptual perspective with emphasis on updates to the 2016 World Health Organization classification. Arch Pathol Lab Med. 2016 Oct;140(10):1026–1037. PubMed PMID: 27684973.
  • Bodmer D, van Den Hurk W, van Groningen JJ, et al. Understanding familial and non-familial renal cell cancer. Hum Mol Genet. 2002 Oct 1;11(20):2489–2498. PubMed PMID: 12351585.
  • Bonne AC, Bodmer D, Schoenmakers EF, et al. Chromosome 3 translocations and familial renal cell cancer. Curr Mol Med. 2004 Dec;4(8):849–854. PubMed PMID: 15579032.
  • Nabi S, Kessler ER, Bernard B, et al. Renal cell carcinoma: a review of biology and pathophysiology. F1000Res. 2018;7:307. PubMed PMID: 29568504; PubMed Central PMCID: PMC5850086.
  • Hsieh JJ, Purdue MP, Signoretti S, et al. Renal cell carcinoma. Nat Rev Dis Primers. 2017 Mar;9(3):17009. PubMed PMID: 28276433; PubMed Central PMCID: PMC5936048.
  • Arjumand W, Sultana S. Role of VHL gene mutation in human renal cell carcinoma. Tumour Biol. 2012 Feb;33(1):9–16. PubMed PMID: 22125026.
  • Mellado B, Gascon P. Molecular biology of renal cell carcinoma. Clin Transl Oncol. 2006 Oct;8(10):706–710. PubMed PMID: 17074668
  • Yang CC, Chu KC, Yeh WM. Expression of vascular endothelial growth factor in renal cell carcinoma is correlated with cancer advancement. J Clin Lab Anal. 2003;17(3):85–89. PubMed PMID: 12696078.
  • Roskoski R Jr. Vascular endothelial growth factor (VEGF) and VEGF receptor inhibitors in the treatment of renal cell carcinomas. Pharmacol Res. 2017 Jun;120:116–132. PubMed PMID: 28330784.
  • Battelli C, Cho DC. mTOR inhibitors in renal cell carcinoma. Therapy. 2011 Jul;8(4):359–367. PubMed PMID: 21894244; PubMed Central PMCID: PMC3164983.
  • Bailey ST, Zhou B, Damrauer JS, et al. mTOR inhibition induces compensatory, therapeutically targetable MEK activation in renal cell carcinoma. PLoS One. 2014;9(9):e104413. PubMed PMID: 25180793; PubMed Central PMCID: PMC4152178.
  • Cancer Genome Atlas Research N. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013 Jul 4;499(7456):43–49. PubMed PMID: 23792563; PubMed Central PMCID: PMC3771322.
  • Lieberthal W, Levine JS. The role of the mammalian target of rapamycin (mTOR) in renal disease. J Am Soc Nephrol. 2009 Dec;20(12):2493–2502. PubMed PMID: 19875810
  • Schultz L, Chaux A, Albadine R, et al. Immunoexpression status and prognostic value of mTOR and hypoxia-induced pathway members in primary and metastatic clear cell renal cell carcinomas. Am J Surg Pathol. 2011 Oct;35(10):1549–1556. PubMed PMID: 21881486; PubMed Central PMCID: PMC3505672.
  • Chen G, Xu JY, Chen J, et al. Loss of PIG3 increases HIF-1alpha level by promoting protein synthesis via mTOR pathway in renal cell carcinoma cells. Oncotarget. 2016 May 10;7(19):27176–27184. PubMed PMID: 27029070; PubMed Central PMCID: PMC5053640.
  • Pal SK, Quinn DI. Differentiating mTOR inhibitors in renal cell carcinoma. Cancer Treat Rev. 2013 Nov;39(7):709–719. PubMed PMID: 23433636; PubMed Central PMCID: PMC4957946.
  • Blank C, Brown I, Peterson AC, et al. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res. 2004 Feb 1;64(3):1140–1145. PubMed PMID: 14871849.
  • Iacovelli R, Nole F, Verri E, et al. Prognostic role of PD-L1 expression in renal cell carcinoma. A systematic review and meta-analysis. Target Oncol. 2016 Apr;11(2):143–148. 10.1007/s11523-015-0392-7. PubMed PMID: 26429561.
  • Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277–1290. PubMed PMID: 29562145; PubMed Central PMCID: PMC5972549.
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252–264. PubMed PMID: 22437870; PubMed Central PMCID: PMC4856023.
  • Ross K, Jones RJ. Immune checkpoint inhibitors in renal cell carcinoma. Clin Sci (Lond). 2017 Nov 1;131(21):2627–2642. PubMed PMID: 29079639; PubMed Central PMCID: PMC5869245.
  • Butz H, Ding Q, Nofech-Mozes R, et al. Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis. Oncotarget. 2018 Jan 12;9(4):4661–4674. PubMed PMID: 29435133; PubMed Central PMCID: PMC5797004.
  • Li S, Yang J, Wang J, et al. Down-regulation of miR-210-3p encourages chemotherapy resistance of renal cell carcinoma via modulating ABCC1. Cell Biosci. 2018;8:9. PubMed PMID: 29445446; PubMed Central PMCID: PMC5803904.
  • Ruan H, Li X, Yang H, et al. Enhanced expression of caveolin-1 possesses diagnostic and prognostic value and promotes cell migration, invasion and sunitinib resistance in the clear cell renal cell carcinoma. Exp Cell Res. 2017 Sep 15;358(2):269–278. PubMed PMID: 28684115.
  • Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017 Jun;15(6):804–834. PubMed PMID: 28596261.
  • Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115–124. PubMed PMID: 17215529.
  • Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061–1068. PubMed PMID: 20100962.
  • Escudier B, Szczylik C, Hutson TE, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Mar 10;27(8):1280–1289. PubMed PMID: 19171708.
  • Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1287–1294. PubMed PMID: 24206640.
  • Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the alliance A031203 CABOSUN trial. J Clin Oncol. 2017 Feb 20;35(6):591–597. PubMed PMID: 28199818; PubMed Central PMCID: PMC5455807.
  • Ivy SP, Wick JY, Kaufman BM. An overview of small-molecule inhibitors of VEGFR signaling. Nat Rev Clin Oncol. 2009 Oct;6(10):569–579. PubMed PMID: 19736552.
  • Schmidinger M. Understanding and managing toxicities of vascular endothelial growth factor (VEGF) inhibitors. EJC Suppl. 2013 Sep;11(2):172–191. PubMed PMID: 26217127; PubMed Central PMCID: PMC4041401.
  • Bhargava P, Robinson MO. Development of second-generation VEGFR tyrosine kinase inhibitors: current status. Curr Oncol Rep. 2011 Apr;13(2):103–111. PubMed PMID: 21318618; PubMed Central PMCID: PMC3047052.
  • Lin B, Song X, Yang D, et al. Anlotinib inhibits angiogenesis via suppressing the activation of VEGFR2, PDGFRbeta and FGFR1. Gene. 2018 May;15(654):77–86. PubMed PMID: 29454091.
  • Sun Y, Niu W, Du F, et al. Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors. J Hematol Oncol. 2016 Oct 4;9(1):105. PubMed PMID: 27716285; PubMed Central PMCID: PMC5051080.
  • Xie C, Wan X, Quan H, et al. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor. Cancer Sci. 2018 Apr;109(4):1207–1219. PubMed PMID: 29446853; PubMed Central PMCID: PMC5891194.
  • Zhong CC, Chen F, Yang JL, et al. Pharmacokinetics and disposition of anlotinib, an oral tyrosine kinase inhibitor, in experimental animal species. Acta Pharmacol Sin. 2018 Apr 5. PubMed PMID: 29620050. DOI:10.1038/aps.2017.199
  • Sun W, Wang Z, Chen R, et al. Influences of anlotinib on cytochrome P450 enzymes in rats using a cocktail method. Biomed Res Int. 2017;2017:3619723. PubMed PMID: 29441353; PubMed Central PMCID: PMC5758843.
  • Zhou AP, Bai YX, Song V, et al. Anlotinib in metastatic renal cell carcinoma (mRCC) with a previous anti-VEGFR TKI: preliminary results from a multicenter, phase II trial. J clin oncol. 2016 May 20;34(15). PubMed PMID: WOS:000404711500056; English.
  • Zhou AP, Ma JH, Bai YX, et al. Anlotinib versus sunitinib as first line treatment for metastatic renal cell carcinoma (mRCC): preliminary results from a randomized phase II clinical trial. J clin oncol. 2016 May 20;34(15). PubMed PMID: WOS:000404665407138; English. DOI:10.1200/Jco.2016.34.15_Suppl.4565
  • Li J, Zhao X, Chen L, et al. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010 Oct 5; 10:529. PubMed PMID: 20923544; PubMed Central PMCID: PMC2984425.
  • Tian S, Quan H, Xie C, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374–1380. PubMed PMID: 21443688.
  • Liu X, Zhang Y, Chen Q, et al. Pharmacokinetic drug interactions of apatinib with rifampin and itraconazole. J Clin Pharmacol. 2017 Oct 2. PubMed PMID: 28967981. DOI:10.1002/jcph.1016
  • Scott LJ. Apatinib: a review in advanced gastric cancer and other advanced cancers. Drugs. 2018 Apr 16. PubMed PMID: 29663291. DOI:10.1007/s40265-018-0903-9
  • Sheng XN, Yan XG, Tang BX, et al. A phase I clinical trial of CM082 (X-82) in combination with everolimus for treatment of metastatic renal cell carcinoma. J clin oncol. 2017 May 20; 35. PubMed PMID: WOS:000411931702075; English. DOI:10.1200/Jco.2017.35.15_Suppl.4575
  • Yan XQ, Sheng XN, Tang BX, et al. Anti-VEGFR, PDGFR, and CSF1R tyrosine kinase inhibitor CM082 (X-82) in combination with everolimus for treatment of metastatic renal cell carcinoma: a phase 1 clinical trial. Lancet Oncol. 2017 Sep;18:S8–S8. PubMed PMID: WOS:000411685800009; English.
  • Moore KN, Jones SF, Kurkjian C, et al. Phase I, first-in-human trial of an oral VEGFR tyrosine kinase inhibitor (TKI) x-82 in patients (pts) with advanced solid tumors. J clin oncol. 2012 May;30(Suppl 15):3041–3041. PubMed PMID: WOS:000318009802397; English. doi:10.1200/jco.2012.30.15_suppl.3041
  • Eskens FA, de Jonge MJ, Bhargava P, et al. Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, −2, and −3 tyrosine kinases, in a 4-week-on, 2-week-off schedule in patients with advanced solid tumors. Clin Cancer Res. 2011 Nov 15;17(22):7156–7163. PubMed PMID: 21976547.
  • Nakamura K, Taguchi E, Miura T, et al. KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties. Cancer Res. 2006 Sep 15;66(18):9134–9142. PubMed PMID: 16982756.
  • Tivozanib hydrochloride in advanced renal cell carcinoma [Internet]. 2013; [cited 2013 May 02]. Available from: https://www.pharmamedtechbi.com/~/media/Supporting%20Documents/The%20Pink%20Sheet%20DAILY/2013/April/tivozanib_AC_Aveo_briefing.pdf
  • Motzer RJ, Nosov D, Eisen T, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol. 2013 Oct 20;31(30):3791–3799. PubMed PMID: 24019545; PubMed Central PMCID: PMC5569677.
  • Motzer RJ, Eisen T, Hutson TE, et al. Overall survival results from a phase III study of tivozanib hydrochloride versus sorafenib in patients with renal cell carcinoma. J clin oncol. 2013 Feb;31(6):350. PubMed PMID: WOS:000333679600348; English.
  • Kim ES. Tivozanib: first global approval. Drugs. 2017 Nov;77(17):1917–1923. PubMed PMID: 28971328.
  • AVEO oncology announces phase 3 TIVO-3 trial of tivozanib in renal cell carcinoma meets primary endpoint [Internet]. Business Wire; 2018. [cited 2018 Nov 28]. Available from: https://bit.ly/2OrdaDy.
  • Patwardhan PP, Ivy KS, Musi E, et al. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget. 2016 Jan 26;7(4):4093–4109. PubMed PMID: 26675259; PubMed Central PMCID: PMC4826192.
  • Bauer TM, Adkins D, Schwartz GK, et al. A first in human phase I study of receptor tyrosine kinase (RTK) inhibitor MGCD516 in patients with advanced solid tumors. J clin oncol. 2016 May 20;34(15): DOI:10.1200/Jco.2016.34.15_Suppl.2575. PubMed PMID: WOS:000404665403174; English.
  • Campbell S, Uzzo RG, Allaf ME, et al. Renal mass and localized renal cancer: AUA guideline. J Urol. 2017 Sep;198(3):520–529. PubMed PMID: 28479239.
  • Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584–3590. PubMed PMID: 19487381; PubMed Central PMCID: PMC3646307.
  • Liu J, Nicum S, Reichardt P, et al. Assessment and management of diarrhea following VEGF receptor TKI treatment in patients with ovarian cancer. Gynecol Oncol. 2018 Jul;150(1):173–179. PubMed PMID: 29627080.
  • Small HY, Montezano AC, Rios FJ, et al. Hypertension due to antiangiogenic cancer therapy with vascular endothelial growth factor inhibitors: understanding and managing a new syndrome. Can J Cardiol. 2014 May;30(5):534–543. PubMed PMID: 24786444.
  • Antoun S, Baracos VE, Birdsell L, et al. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol. 2010 Aug;21(8):1594–1598. PubMed PMID: 20089558.
  • Huillard O, Mir O, Peyromaure M, et al. Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients. Br J Cancer. 2013 Mar 19;108(5):1034–1041. PubMed PMID: 23462722; PubMed Central PMCID: PMC3619075.
  • de Jesus-Gonzalez N, Robinson E, Moslehi J, et al. Management of antiangiogenic therapy-induced hypertension. Hypertension. 2012 Sep;60(3):607–615. PubMed PMID: 22851729; PubMed Central PMCID: PMC3421063.
  • Fan L, Iseki S. Immunohistochemical localization of vascular endothelial growth factor in the endocrine glands of the rat. Arch Histol Cytol. 1998 Mar;61(1):17–28. PubMed PMID: 9557964
  • Shen G, Zheng F, Ren D, et al. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol. 2018 Sep 19;11(1):120. PubMed PMID: 30231931; PubMed Central PMCID: PMC6146601.
  • Andreyev J, Ross P, Donnellan C, et al. Guidance on the management of diarrhoea during cancer chemotherapy. Lancet Oncol. 2014 Sep;15(10):e447–e460. PubMed PMID: 25186048.
  • Jackson KD, Durandis R, Vergne MJ. Role of cytochrome P450 enzymes in the metabolic activation of tyrosine kinase inhibitors. Int J Mol Sci. 2018 Aug 11;19(8). PubMed PMID: 30103502; PubMed Central PMCID: PMC6121577. DOI:10.3390/ijms19082367
  • Teo YL, Ho HK, Chan A. Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations. Br J Clin Pharmacol. 2015 Feb;79(2):241–253. PubMed PMID: 25125025; PubMed Central PMCID: PMC4309630.
  • Clarke JM, Hurwitz HI. Understanding and targeting resistance to anti-angiogenic therapies. J Gastrointest Oncol. 2013 Sep;4(3):253–263. PubMed PMID: 23997938; PubMed Central PMCID: PMC3712298.
  • Gossage L, Eisen T. Targeting multiple kinase pathways: a change in paradigm. Clin Cancer Res. 2010 Apr 1;16(7):1973–1978. PubMed PMID: 20215532; PubMed Central PMCID: PMC2875112.
  • Atkins MB, Plimack ER, Puzanov I, et al. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 2018 Mar;19(3):405–415. PubMed PMID: 29439857.
  • Choueiri TK, Larkin J, Oya M, et al. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol. 2018 Apr;19(4):451–460. PubMed PMID: 29530667.
  • Weinstock M, McDermott D. Targeting PD-1/PD-L1 in the treatment of metastatic renal cell carcinoma. Ther Adv Urol. 2015 Dec;7(6):365–377. PubMed PMID: 26622321; PubMed Central PMCID: PMC4647139.
  • Motzer RJ, Penkov K, Haanen JBAG, et al. LBA6_PRJAVELIN renal 101: a randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). Ann Oncol. 2018;29(suppl_8):mdy424.036–mdy424.036.
  • Pena C, Lathia C, Shan M, et al. Biomarkers predicting outcome in patients with advanced renal cell carcinoma: results from sorafenib phase III treatment approaches in renal cancer global evaluation trial. Clin Cancer Res. 2010 Oct 1;16(19):4853–4863. PubMed PMID: 20651059.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.