SCIENCE@home

The Association of Alternate VEGF Ligands with Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer

C. Lieu,H. Tran,Zhi-qin Jiang,M. Mao,M. Overman,E. Lin,C. Eng,Jeffrey S. Morris,L. Ellis,J. Heymach,S. Kopetz

Published 2013 in PLoS ONE

ABSTRACT

Background Circulating angiogenic factors are altered in patients with mCRC receiving bevacizumab. Evaluation of alterations in levels of VEGF ligands may provide insights into possible resistance mechanisms. Methods PlGF, VEGF-A, VEGF-C, and VEGF-D were measured from two cohorts of patients. Sequential plasma samples were obtained from a discovery cohort of 42 patients treated with chemotherapy and bevacizumab. A validation cohort included plasma samples from a cross-sectional of 403 patients prior to chemotherapy, or after progression on a regimen with or without bevacizumab. Results In the discovery cohort, VEGF-C was increased prior to progression and at progression (+49% and +95%, respectively, p<0.01), consistent with previously reported elevations in PlGF. Levels of VEGF-D were increased (+23%) at progression (p=0.05). In the validation cohort, samples obtained from patients after progression on a regimen with bevacizumab had higher levels of PlGF and VEGF-D (+43% and +6%, p=0.02, p=0.01, respectively) compared to untreated patients, but failed to validate the increase in VEGF-C seen in the first cohort. Patients who progressed on chemotherapy with bevacizumab had significantly elevated levels of PlGF (+88%) but not VEGF-C and VEGF-D compared to patients treated with chemotherapy alone. Elevations of PlGF and VEGF-D appeared transient and returned to baseline with a half-life of 6 weeks. Conclusions Increases in PlGF and VEGF-D were observed after progression on chemotherapy with bevacizumab. These changes appear to be reversible after discontinuing therapy. These ligands are associated with resistance to bevacizumab-containing chemotherapy in mCRC, but causation remains to be established.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-36 of 36 references · Page 1 of 1

CITED BY

Showing 1-100 of 133 citing papers · Page 1 of 2

12
Next