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In the treatment of aRCC,

Patients will face the challenge of VEGFR-TKI progression1,2

There are multiple potential mechanisms of resistance in advanced RCC3

These potential mechanisms of resistance can include:

Potential mechanisms of VEGFR-TKI resistance

Resistance activity in VEGF-inhibited endothelial cells.

  • Similar mechanisms of resistance to mTOR inhibitors may exist, as well as compensatory activation of PI3 kinase and AKT4

Acquired resistance that may develop after VEGFR-TKI treatment results in multiple escape and hyperactivated pathways5

  • The mTOR pathway continues to be activated after VEGFR-TKI progression5,6
Abbreviations:
aRCC, advanced renal cell carcinoma; mTOR, mammalian target of rapamycin; VEGFR-TKI, vascular endothelial growth factor receptor-tyrosine kinase inhibitor.
References:
  1. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 2008;8(8):592-603.
  2. Guida M, Colucci G. The next challenge in the treatment of renal cell carcinoma: overcoming resistance mechanisms to antiangiogenic agents. In Amato RJ, ed. Emerging Research and Treatments in Renal Cell Carcinoma. InTech: Rijeka, Croatia; 2012:83-98.
  3. Vasudev NS, Larkin JMG. Tyrosine kinase inhibitors in the treatment of advanced renal cell carcinoma: focus on pazopanib. Clin Med Insights Oncol. 2011;5:333-342.
  4. Rini BI, Flahery K. Clinical effect and future considerations for molecularly-targeted therapy in renal cell carcinoma. Urol Oncol. 2008;26:543-549.
  5. Sakai I, Miyake H, Fujisawa M. Acquired resistance to sunitinib in human renal cell carcinoma cells is mediated by constitutive activation of signal transduction pathways associated with tumor cell proliferation. BJU Int. 2013;112(2):E211-E220.
  6. AFINITOR [summary of product characteristics]. Novartis Pharma AG; 2016.