Significance of tumor microenvironment in acquiring resistance to vascular endothelial growth factor-tyrosine kinase inhibitor and recent advance of systemic treatment of clear cell renal cell carcinoma

Shuji Mikami, Ryuichi Mizuno, Takeo Kosaka, Nobuyuki Tanaka, Naoto Kuroda, Yoji Nagashima, Yasunori Okada, Mototsugu Oya

Research output: Contribution to journalReview article

Abstract

The development of systemic therapies, including vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI) and mammalian target of rapamycin (mTOR) inhibitors, represents a major breakthrough in the treatment of patients with renal cell carcinoma (RCC). However, inherent resistance is observed in some patients and acquired resistance commonly develops in many patients within several months of the initiation of systemic therapies. Since these treatments rarely cure patients, their aim is to suppress tumor progression and prolong survival. Therefore, the establishment of dependable criteria that predict responses and resistance to systemic therapies is clinically important, and the underlying molecular mechanisms also need to be elucidated for the future development of more effective therapies. We herein review recent advances in research on the molecular mechanisms underlying resistance, with a focus on morphological characteristics, tumor angiogenesis, and the tumor immune microenvironment in RCC and their relationships with VEGF-TKI treatments. Recent therapies using immune checkpoint inhibitors (ICI) and newly developed VEGF-TKI also appear to be effective for advanced RCC, with stable and durable responses to ICI being observed in some RCC patients. These new drugs and their outcomes have been briefly described.

Original languageEnglish
JournalPathology international
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • VEGF-TKI
  • angiogenesis
  • immunotherapy
  • molecular target therapy
  • renal cell carcinoma
  • resistance
  • tumor microenvironment

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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