Challenges for patient selection with VEGF inhibitors

R. Longo, G. Gasparini

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

As targeted therapies for cancer become increasingly integrated into standard practice, appropriate selection of the patients most likely to benefit from these therapies is now receiving critical scrutiny. Early experience with therapies directed at targets that are definitively overactive (e.g. the bcr-abl tyrosine kinase targeted by imatinib) or over-expressed [e.g. the human epidermal growth factor receptor 2 (HER2) targeted by trastuzumab] has generated the perception that pre-treatment target assessment is a pre-requisite for therapy with all targeted agents. However, emerging evidence suggests that this is not presently feasible for anti-angiogenic agents. Despite considerable evidence for the association of intratumoral and/or plasma vascular endothelial growth factor (VEGF) levels with tumor progression and/or poor prognosis, pre-treatment VEGF levels do not appear to be predictive of response to anti-angiogenic therapy. This may possibly be due to the complexity of the angiogenic pathways and the limitations associated with current methods of VEGF detection and quantification; e.g. low assay sensitivity and lack of standardized methods could prevent detection of very small increases in VEGF, which may be clinically important in patients with tumors that are highly dependent on this growth factor. In addition to a general lack of agreement as to the relative clinical relevance of circulating versus tumor VEGF levels, the absence of a 'gold standard' VEGF detection assay and the lack of a predefined, clinically relevant cut-off pose a significant hindrance to the clinical utility of VEGF measurements for therapy selection. Given the fundamental importance of angiogenesis for tumor growth and progression, and the key role of VEGF in these processes, presently it seems appropriate to view anti-VEGF agents such as bevacizumab (Avastin®) as having potential utility, independently of pre-treatment screening. Further research is needed to define the relationship between potential surrogate markers of VEGF pathway activity and clinical outcomes.

Original languageEnglish
Pages (from-to)151-170
Number of pages20
JournalCancer Chemotherapy and Pharmacology
Volume60
Issue number2
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Patient Selection
Vascular Endothelial Growth Factor A
Tumors
Therapeutics
Neoplasms
Assays
bcr-abl Fusion Proteins
Critical Pathways
Intercellular Signaling Peptides and Proteins
Screening
Biomarkers
Association reactions
Plasmas
Growth
Research

Keywords

  • Angiogenesis
  • Bevacizumab
  • Epidermal growth factor receptor
  • Patient selection
  • Vascular endothelial growth factor
  • Vatalanib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

Cite this

Challenges for patient selection with VEGF inhibitors. / Longo, R.; Gasparini, G.

In: Cancer Chemotherapy and Pharmacology, Vol. 60, No. 2, 07.2007, p. 151-170.

Research output: Contribution to journalArticle

Longo, R. ; Gasparini, G. / Challenges for patient selection with VEGF inhibitors. In: Cancer Chemotherapy and Pharmacology. 2007 ; Vol. 60, No. 2. pp. 151-170.
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