VEGF pathway targeting agents, vessel normalization and tumor drug uptake: From bench to bedside

Marlous Arjaans, Carolien P. Schröder, Sjoukje F. Oosting, Urania Dafni, Josee E. Kleibeuker, E. G. E. de Vries*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

91 Citations (Scopus)
273 Downloads (Pure)

Abstract

Vascular endothelial growth factor (VEGF) pathway targeting agents have been combined with other anticancer drugs, leading to improved efficacy in carcinoma of the cervix, stomach, lung, colon and rectum, ovary, and breast. Vessel normalization induced by VEGF pathway targeting agents influences tumor drug uptake. Following bevacizumab treatment, preclinical and clinical studies have shown a decrease in tumor delivery of radiolabeled antibodies and two chemotherapeutic drugs. The decrease in vessel pore size during vessel normalization might explain the decrease in tumor drug uptake. Moreover, the addition of bevacizumab to cetuximab, or panitumumab in colorectal cancer patients or to trastuzumab in breast cancer patients, did not improve efficacy. However, combining bevacizumab with chemotherapy did increase efficacy in some cancer types. Novel biomarkers to select patients who may benefit from combination therapies, such as the effect of an angiogenesis inhibitor on tumor perfusion, requires innovative trial designs and large clinical trials. Small imaging studies with radiolabeled drugs could be used in the interphase to gain further insight into the interplay between VEGF targeted therapy, vessel normalization and tumor drug delivery.

Original languageEnglish
Pages (from-to)21247-21258
Number of pages12
JournalOncotarget
Volume7
Issue number16
DOIs
Publication statusPublished - 19-Apr-2016

Keywords

  • antiangiogenic drugs
  • blood vessel normalization
  • tumor drug delivery
  • METASTATIC COLORECTAL-CANCER
  • CELL LUNG-CANCER
  • PHASE-III TRIAL
  • NEWLY-DIAGNOSED GLIOBLASTOMA
  • BREAST-CANCER
  • DOUBLE-BLIND
  • ANTIANGIOGENIC THERAPY
  • 1ST-LINE TREATMENT
  • GROWTH-FACTOR
  • VASCULAR NORMALIZATION

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