Biomarkers of reactive resistance and early disease progression during chemotherapy plus bevacizumab treatment for colorectal carcinoma

Hidetoshi Hayashi, Tokuzo Arao, Kazuko Matsumoto, Hideharu Kimura, Yosuke Togashi, Yoshinori Hirashima, Yosuke Horita, Satoru Iwasa, Natsuko Tsuda Okita, Yoshitaka Honma, Atsuo Takashima, Ken Kato, Tetsuya Hamaguchi, Yasuhiro Shimada, Kazuhiko Nakagawa, Kazuto Nishio, Yasuhide Yamada

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Molecular markers for predicting or monitoring the efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) remain to be identified. We have now measured the serum concentrations of 25 angiogenesis-related molecules with antibody suspension bead array systems for 25 mCRC patients both before and during treatment in a previously reported phase II trial of FOLFIRI chemotherapy plus bevacizumab. The serum concentration of vascular endothelial growth factor-A (VEGF-A) decreased after the onset of treatment (P < 0.0001), whereas that of placental growth factor increased (P < 0.0001). Significant differences in the levels of several factors (such as VEGF-A, soluble VEGF receptor-2, and interleukin-8) were apparent between responders and nonresponders during treatment. The rapid and pronounced decrease in serum VEGF-A level after treatment onset was apparent in all subjects and was independent of the baseline concentration. However, four of nine nonresponders showed a subsequent early increase in the serum VEGF-A level. Our results thus suggest that an early increase in the serum VEGF-A concentration after the initial decrease is a potential predictive marker of a poor response and reactive resistance to bevacizumab plus chemotherapy.

Original languageEnglish
Pages (from-to)2588-2595
Number of pages8
JournalOncotarget
Volume5
Issue number9
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Angiogenesis
  • Bevacizumab
  • Colorectal carcinoma
  • Placental growth factor (PlGF)
  • Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'Biomarkers of reactive resistance and early disease progression during chemotherapy plus bevacizumab treatment for colorectal carcinoma'. Together they form a unique fingerprint.

Cite this