Serial measurements of serum PDGF-AA, PDGF-BB, FGF2, and VEGF in multiresistant ovarian cancer patients treated with bevacizumab

Abstract

IntroductionAnti-VEGF treatment has proven effective in recurrent ovarian cancer. However, the identification of the patients most likely to respond is still pending. It is well known that the angiogenesis is regulated by several other pro-angiogenic proteins, e.g. the platelet - derived growth factor (PDGF) system and the fibroblast growth factor (FGF) system. These other signaling pathways may remain active or become upregulated during anti-VEGF treatment.The aim of the present study was to investigate if potential changes of PDGF-BB, PDGF-AA, and FGF2 before and during bevacizumab treatment had predictive value for early progression or survival. Furthermore, we wanted to investigate the importance of serum VEGF in the same cohort.MethodsThis study included 106 patients with chemotherapy-resistant epithelial ovarian cancer who were treated with single agent bevacizumab as part of a biomarker protocol. Patients were evaluated for response by the Response Evaluation Criteria In Solid Tumors (RECIST) and/ or Gynecologic Cancer Intergroup (GCIG) CA125 criteria. Serum samples were collected at baseline and prior to each treatment. FGF2, PDGF-BB, PDGF-AA were quantified simultaneously using the Luminex system, and VEGF-A was measured by ELISA. Eighty-eight baseline samples were avaliable for FGF2, PDGF-BB, PDGF-AA analysis, and 93 baseline samples for VEGF.ResultsHigh baseline serum VEGF was related to poor overall survival. Furthermore, high serum PDGF-BB and FGF2 was of prognostic significance. None of the markers showed predictive value, neither at baseline level nor during the treatment.

Proliferation and maturation of intratumoral blood vessels in women with malignant ovarian tumors assessed with cancer stem cells marker nestin and platelet derived growth factor PDGF-B

“…Emerging evidence suggests that the PDGF system plays an essential role in ovarian cancer progression [22]. Still, there are only few published studies on PDGF-B expression in ovarian malignancies [23,24]. Our results confirmed that in women with ovarian cancer the sources of PDGF-B could be both tumor cells and endothelial cell/pericytes.…”

“…However, in stromal cells 40% of their cases stained positive for PDGFR-α. In another study from the same group Madsen et al [24] have measured serum PDGF-AA, PDGF-BB, FGF2, and VEGF concentrations in bevacizumab treated multiresistant ovarian cancer patients. The levels of these cytokines were up-regulated in ovarian cancer and were associated with stage and residual disease.…”

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

“…Many novel VEGF/VEGFR-targeted inhibitors have been reported to improve the prognosis and survival of patients more than chemotherapy alone does 42 , such as bevacizumab and ramucirumab [43][44][45] . However, when VEGF signaling is blocked, other compensatory angiogenic signaling pathways can regulate tumor angiogenesis, including the PDGF, FGF, and hepatocyte growth factor/Met signaling pathways 46 . Consequently, multi-agent therapy appears to be the optimal strategy for targeting angiogenesis.…”

Expression of growth-regulated oncogene-1, hepatocyte growth factor, platelet-derived growth factor-AA and soluble E-selectin and their association with high-risk human papillomavirus infection in squamous cell carcinoma of the uterine cervix

“…Our findings suggested that GRO-1 and sE-selectin may have an impact on the prognosis of CSCC patients by affecting FIGO stage or lymph node metastasis, thus GRO-1 and sE-selectin were not independent prognostic risk factors. Madsen et al (44) failed to verify the prognostic value of PDGF-AA in ovarian cancer. However, another study indicated the adverse prognosis of PDGF-AA in pancreatic cancer (26), thus the prognostic value of PDGF-AA in CSCC requires further investigation.…”