Circulating VEGF and eNOS variations as predictors of outcome in metastatic colorectal cancer patients receiving bevacizumab

Marisi, Giorgia; Scarpi, Emanuela; Passardi, Alessandro; Nanni, Oriana; Ragazzini, Angela; Valgiusti, Martina; Casadei-Gardini, Andrea; Neri, Luca M.; Frassineti, Giovanni Luca; Amadori, Dino; Ulivi, Paola

doi:10.1038/s41598-017-01420-0

Cited by 26 publications

(28 citation statements)

References 30 publications

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“…The fact that high baseline VEGF-A and PlGF levels in patients treated with placebo are associated with poor outcomes is supported by previous reports (42)(43)(44). High VEGF-A serum levels (>5.1 pg/mL) at baseline were associated with worse OS and PFS in patients with mCRC who received either mFOLFOX6 or FOLFIRI with first-line bevacizumab (44).…”

Section: Discussionmentioning

confidence: 63%

Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial

Cutsem

Paccard

Chiron

et al. 2020

Clinical Cancer Research

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Purpose: Aflibercept is a targeted anti-VEGF therapy used to treat patients with metastatic colorectal cancer (mCRC) following progression on oxaliplatin-based regimens. This post hoc study evaluated the effect of prior bevacizumab treatment and growth factor levels on patient outcomes associated with aflibercept in the VELOUR phase III trial. Experimental Design: Baseline biomarker plasma concentrations were measured using a bead-based multiplex assay. Patients were grouped according to prior bevacizumab treatment, secondline treatment, and serum biomarker concentrations, and analyzed for overall survival (OS) and progression-free survival (PFS). Results: Plasma samples were available for 553 patients (placebo n ¼ 265; aflibercept n ¼ 288), of which 169 had received prior bevacizumab. Nine biomarkers implicated in angiogenesis or bevacizumab resistance correlated with prior bevacizumab therapy. VEGF-A and placental growth factor (PlGF) were the most significantly increased in patients who had received prior bevacizumab compared with those who had not received prior bevacizumab. In the placebo group, patients with high VEGF-A (>144 pg/mL) levels at baseline had worse OS and PFS compared with patients with lower levels at baseline (9.6 vs. 12.9 months). This was also seen in patients who received placebo and had high baseline PlGF (>8 pg/mL; 9.7 vs. 11.7 months). In the aflibercept group, prolonged OS and PFS were observed regardless of baseline VEGF-A or PlGF levels. Conclusions: High VEGF-A and PlGF serum levels may underlie development of resistance to bevacizumab in patients with mCRC. Aflibercept retains its activity regardless of baseline VEGF-A and PlGF levels and may be an effective second-line treatment for patients with bevacizumab-induced resistance.

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Section: Discussionmentioning

confidence: 63%

Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial

Cutsem

Paccard

Chiron

et al. 2020

Clinical Cancer Research

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“…This was consistent with the observation that L-NIO (a NOS3 inhibitor) inhibited cell growth and angiogenesis in colorectal cancer, and the anti-tumour effect of E7080 (lenvatinib) could be increased after combination with L-NIO in colorectal cancer (31,32). Although the analyses of NOS3 expression from the current TCGA data was not statistically relevant to the prognosis in COAD patients, Marisi et al found that the NOS3 expression level affected the progression-free survival and overall survival (OS) of metastatic colorectal cancer patients (9). In PRAD, NOS3 expression was higher in tumour tissues, but did not signi cantly affect overall survival (stage data could not be accessed).…”

Section: Discussionmentioning

confidence: 93%

“…In addition, L-NIO could promote the anti-tumour effect of lenvatinib (31,32). The NOS3 level was signi cantly correlated with outcomes of bevacizumab-based chemotherapy in COAD (9,35). Unfortunately, bevacizumab, L-NIO, and L-NAME were not included in the CTRP database.…”

Section: Discussionmentioning

confidence: 99%

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Abnormal Expression of NOS3 and Association with Clinical Outcome are Highly Cancer Dependent as Revealed through Pan-Cancer Analysis

Zou¹,

Lv²,

Yang³

et al. 2019

Preprint

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Background: NOS3 (endothelial NOS, eNOS) is a member of the nitric oxide synthase (NOS) enzyme family, mainly participating in nitric oxide (NO) generation. NOS3 has been reported to inhibit apoptosis and promote angiogenesis, proliferation, and invasiveness. However, the expression pattern of NOS3 and its diagnostic and prognostic potential has not been investigated in a pan-cancer perspective. Methods: In this research, data from the Genotype-Tissue Expression (GTEx), the Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP) were employed and NOS3 expression was comprehensively analysed in normal tissues, cancer tissues and cell lines. Its relationship with clinical phenotypes and drug responses was also analysed. Results: In normal tissues, NOS3 was expressed at the highest levels in the spleen and the lowest levels in the blood. Compared with the corresponding normal tissues, its expression in tumour was significantly increased in seven tumour types but decreased in eight tumour types. And NOS3 expression was positively or negatively related to tumour stage and overall survival of patients depending on the tumour types. The expression of NOS3 was related to the response to ‘SR8278’. Conclusions: NOS3 was differentially expressed in tumour tissues, and had prognosis value in some tumour types. And its correlation to drug response warrants further investigation.

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“…This finding corroborates our hypothesis that the removal of the primary tumor brings several theoretical advantages. Tumoral cells produce high quantities of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), which can also be found in the blood circulation (45). These growth factors could have a stimulatory action on the liver metastases, neutralizing the action of the biological chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Resection or Stenting in the Treatment of Symptomatic Advanced Metastatic Rectal Cancer: A Dilemma

et al. 2019

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Background/Aim: Patients affected with Stage IV colorectal cancer and unresectable metastases represent a heterogeneous group. Resection of the primary tumor or stent positioning followed by chemotherapy and/or targeted therapies still represent a difficult choice for surgeons. Patients and Methods: From February 2013 to September 2019, 46 patients were enrolled into a prospective randomized open label parallel trial presenting with Stage IVA and IVB rectal cancer, unresectable metastases and symptoms of subacute large bowel obstruction. Our population was divided into two groups: Group 1 included 20 patients who underwent placement of a self-expandable metal stent and Group 2 included 26 patients in whom primary tumor resection was performed. Results: Oneyear actuarial survival rate of Group 1 was significantly lower compared to Group 2. Overall 17 patients had survival longer than 1-year (3 in Group 1 and 14 in Group 2). Cox regression analysis showed that endoscopic stent positioning and the suspension of the chemotherapy because of deterioration of liver function tests were the two most important factors negatively influencing survival. Conclusion: Patients affected with stage IVA and IVB rectal cancer and symptoms of bowel obstruction had a significant longer survival rate when submitted to surgical rectal resection followed by chemotherapy. Colorectal cancer is a commonly diagnosed cancer. More than 25% of the patients have an initial diagnosis at a Stage IV, with a 5-year overall survival ranging from 10 to 18% (1).

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Circulating VEGF and eNOS variations as predictors of outcome in metastatic colorectal cancer patients receiving bevacizumab

Cited by 26 publications

References 30 publications

Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial

Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial

Abnormal Expression of NOS3 and Association with Clinical Outcome are Highly Cancer Dependent as Revealed through Pan-Cancer Analysis

Resection or Stenting in the Treatment of Symptomatic Advanced Metastatic Rectal Cancer: A Dilemma

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