Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Novel concepts of antiangiogenic therapies in metastatic renal cell cancer

Novel concepts of antiangiogenic therapies in metastatic renal cell cancer The era of antiangiogenic drugs targeting the vascular endothelial growth factor (VEGF) signaling pathway has become a mainstay in the treatment of metastatic renal cell carcinoma (mRCC), showing primary responses in 65–70% of patients. Nevertheless, most of those patients progress to angiogenesis inhibitors over time due to different modes of resistance (adaptive and intrinsic). Both in vitro and in vivo analyses provided evidence that PD-L1 upregulation in hypoxia conditions is dependent on hypoxia-inducible factor (HIF)-2alpha and is associated with an overexpression of VEGF. Thus, additional blockade of PD-L1 along with inhibition of angiogenesis pathways seems to represent a novel and innovative treatment concept in mRCC. In this short review, we provide an overview on ongoing phase III trials combining antiangiogenic therapies with checkpoint inhibitors in the first-line setting. Moreover, we critically analyze the impact of recently approved therapeutic antiangiogenic agents and checkpoint inhibitors after progression to first-generation tyrosine kinase inhibitors and their mode of action. In addition, response and resistance hypotheses and biomarkers to antiangiogenic therapy in clinical practice are critically discussed. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png memo - Magazine of European Medical Oncology Springer Journals

Novel concepts of antiangiogenic therapies in metastatic renal cell cancer

Download PDF
7 pages

Loading next page...
 
/lp/springer-journals/novel-concepts-of-antiangiogenic-therapies-in-metastatic-renal-cell-fGBlPLfSvb
Publisher
Springer Journals
Copyright
Copyright © 2017 by The Author(s)
Subject
Medicine & Public Health; Oncology; Medicine/Public Health, general
ISSN
1865-5041
eISSN
1865-5076
DOI
10.1007/s12254-017-0344-2
Publisher site
See Article on Publisher Site

Abstract

The era of antiangiogenic drugs targeting the vascular endothelial growth factor (VEGF) signaling pathway has become a mainstay in the treatment of metastatic renal cell carcinoma (mRCC), showing primary responses in 65–70% of patients. Nevertheless, most of those patients progress to angiogenesis inhibitors over time due to different modes of resistance (adaptive and intrinsic). Both in vitro and in vivo analyses provided evidence that PD-L1 upregulation in hypoxia conditions is dependent on hypoxia-inducible factor (HIF)-2alpha and is associated with an overexpression of VEGF. Thus, additional blockade of PD-L1 along with inhibition of angiogenesis pathways seems to represent a novel and innovative treatment concept in mRCC. In this short review, we provide an overview on ongoing phase III trials combining antiangiogenic therapies with checkpoint inhibitors in the first-line setting. Moreover, we critically analyze the impact of recently approved therapeutic antiangiogenic agents and checkpoint inhibitors after progression to first-generation tyrosine kinase inhibitors and their mode of action. In addition, response and resistance hypotheses and biomarkers to antiangiogenic therapy in clinical practice are critically discussed.

Journal

memo - Magazine of European Medical Oncology – Springer Journals

Published: Aug 11, 2017

References

  • Cancer statistics
    Siegel, RL; Miller, KD; Jemal, A
  • Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): A literature review
    Gupta, K; Miller, JD; Li, JZ; Russell, MW
  • Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: A multi-center European study
    Cindolo, L; Patard, JJ; Chiodini, P
  • Cabozantinib: an active novel multikinase inhibitor in renal cell carcinoma
    Tannir, NM; Schwab, G; Grünwald, V
  • Modes of resistance to anti-angiogenic therapy
    Bergers, G; Hanahan, D
  • Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer
    Welti, J; Loges, S; Dimmeler, S; Carmeliet, P
  • Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma
    Zhou, L; Liu, XD; Sun, M
  • Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: Implications for antiangiogenic drugs as chemosensitizing agents
    Shaked, Y; Henke, E; Roodhart, JM; Mancuso, P
  • New strategies in kidney cancer: therapeutic advances through understanding the molecular basis of response and resistance
    Rini, BI
  • Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies
    Pircher, A; Jöhrer, K; Kocher, F
  • hypertension following anti-angiogenesis therapy
    Biomarkers, RBI
  • Magnetic resonance imaging-measured blood flow change after antiangiogenic therapy with PTK787/ZK 222584 correlates with clinical outcome in metastatic renal cell carcinoma
    Bazelaire, C; Alsop, DC; George, D
  • Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib
    Nikolinakos, PG; Altorki, N; Yankelevitz, D
  • CXCL12 expression and PD-L1 expression serve as prognostic biomarkers in HCC and are induced by hypoxia
    Semaan, A; Dietrich, D; Bergheim, D
  • Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage I pulmonary squamous cell carcinoma
    Yang, CY; Lin, MW; Chang, YL; Wu, CT; Yang, PC
  • Renal cell carcinoma programmed death-ligand 1, a new direct target of hypoxia-induciblefactor-2 Alpha, is regulated by von Hippel-Lindau gene mutation status
    Messai, Y; Gad, S; Noman, MZ
  • PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation
    Noman, MZ; Desantis, G; Janji, B
  • Targeting hypoxia at the forefront of anticancer immune responses
    Noman, MZ; Chouaib, S
  • Up-regulation of hypoxia-inducible factors HIF-1alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function
    Krieg, M; Haas, R; Brauch, H; Acker, T; Flamme, I; Plate, KH
  • PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma
    Ruf, M; Moch, H; Schraml, P
  • Clinicopathologic analysis of PD-L1 and PD-L2 expression in renal cell carcinoma: Association with oncogenic proteins status
    Shin, SJ; Jeon, YK; Kim, PJ
  • c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma
    Gibney, GT; Aziz, SA; Camp, RL
  • MET expression and copy number status in clear-cell renal cell carcinoma: prognostic value and potential predictive marker
    Macher-Goeppinger, S; Keith, M; Endris, V
  • Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial
    Choueiri, TK; Escudier, B; Powles, T
  • Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage
    Yamamoto, Y; Matsui, J; Matsushima, T
  • Targeting of tumor growth and Angiogenesis underlies the enhanced Antitumor activity of Lenvatinib in combination with Everolimus
    Matsuki, M; Adachi, Y; Ozawa, Y
  • A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC)
    Molina, AM; Hutson, TE; Larkin, J
  • Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: A randomised, phase 2, open-label, multicentre trial
    Motzer, RJ; Hutson, TE; Glen, H
  • Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
    Escudier, B; Porta, C; Schmidinger, M
  • Nivolumab for metastatic renal cell carcinoma: Results of a randomized phase II trial
    Motzer, RJ; Rini, BI; McDermott, DF
  • Nivolumab versus Everolimus in advanced renal-cell carcinoma
    Motzer, RJ; Escudier, B; McDermott, DF
  • Checkmate 025 randomized phase 3 study: outcomes by key baseline factors and prior therapy for Nivolumab versus Everolimus in advanced renal cell carcinoma
    Escudier, B; Sharma, P; McDermott, DF
  • Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimusin CheckMate 025: A randomised, open-label, phase 3 trial
    Cella, D; Grünwald, V; Nathan, P