Refractory mechanisms

Mototsugu Oya, Toshiaki Shinojima, Ryuichi Mizuno

Research output: Chapter in Book/Report/Conference proceedingChapter


Vascular endothelial growth factor (VEGF)-targeted agents have brought significant progress in pharmacotherapy of advanced renal cell carcinoma (RCC). Some RCCs, however, appear to have innate resistance to treatment. Moreover, majority of patients who primarily respond to VEGF-targeted therapy eventually develop disease progression after prolonged treatment. The mechanism of resistance is supposed to be so multifactorial that it cannot be explained by single molecular events. Despite various factors including cytokines, bone marrowderived cells, microenvironment, and genetic or epigenetic abnormality could be involved, tumor hypoxia seems to play one of crucial roles in most of the processes. The multiple mechanism in developing drug resistance might just represent the diversity of cellular response to hypoxia and nutrient deprivation, induced by the disruption of the blood vessels. In this chapter we comprehensively review current efforts aiming to clarify these process and to develop pharmacological strategies leading to overcome the drug resistance in RCC.

Original languageEnglish
Title of host publicationRenal Cell Carcinoma
Subtitle of host publicationMolecular Features and Treatment Updates
PublisherSpringer Japan
Number of pages17
ISBN (Electronic)9784431555315
ISBN (Print)9784431555308
Publication statusPublished - 2017 Jan 1


  • Acquired resistance
  • Antiangiogenic therapy
  • Intrinsic resistance
  • Mechanisms of drug resistance
  • Renal cell carcinoma

ASJC Scopus subject areas

  • General Medicine
  • General Biochemistry,Genetics and Molecular Biology


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