Biomarkers of reactive resistance and early disease progression during chemotherapy plus bevacizumab treatment for colorectal carcinoma

Abstract

Molecular markers for predicting or monitoring the efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) remain to be identified. We have now measured the serum concentrations of 25 angiogenesis-related molecules with antibody suspension bead array systems for 25 mCRC patients both before and during treatment in a previously reported phase II trial of FOLFIRI chemotherapy plus bevacizumab. The serum concentration of vascular endothelial growth factor–A (VEGF-A) decreased after the onset of treatment (P < 0.0001), whereas that of placental growth factor increased (P < 0.0001). Significant differences in the levels of several factors (such as VEGF-A, soluble VEGF receptor–2, and interleukin-8) were apparent between responders and nonresponders during treatment. The rapid and pronounced decrease in serum VEGF-A level after treatment onset was apparent in all subjects and was independent of the baseline concentration. However, four of nine nonresponders showed a subsequent early increase in the serum VEGF-A level. Our results thus suggest that an early increase in the serum VEGF-A concentration after the initial decrease is a potential predictive marker of a poor response and reactive resistance to bevacizumab plus chemotherapy.

Genetic variants in CCL5 and CCR5 genes and serum VEGF‐A levels predict efficacy of bevacizumab in metastatic colorectal cancer patients

“…Thereby, our exploratory analysis demonstrated that levels of other angiogenic factors at baseline did not correlate with outcome, while interestingly they could be changed under administration of BEV. In previous reports, blood concentrations of several angiogenic factors significantly increased prior to radiological disease progression or were higher in responders compared to non‐responders at various points during BEV treatment . Such phenomena are consistent with our results: decrease in serum IL‐8 levels is expected to achieve a better clinical outcome as shown in the CCL5 rs2280789 G/G variant, and a modest increase of PlGF marked in any CCR5 rs1799988 T allele than the C/C is also expected to provide a better outcome.…”

Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers

“…30 Interleukin 8 is a proinflammatory cytokine related to ocular angiogenesis and to increased vascular permeability. 31 In an investigation of biomarkers related to cancer resistance to bevacizumab, Hayashi et al 32 detected higher serum concentrations of interleukin 8, angiopoietin 2, and VEGF-C in nonresponders compared with responders to bevacizumab.…”

Serum VEGF-A and CCL5 levels as candidate biomarkers for efficacy and toxicity of regorafenib in patients with metastatic colorectal cancer

“…Recently, some studies reported the correlation between tumor-related markers in blood association with treatment efficacy by chemotherapy [25, 26]. Hayashi et al demonstrated that an early increase in the serum VEGF-A concentration after the initial decrease is a potential predictive marker of poor tumor response in the second-line FOLFIRI plus bevacizumab for metastatic CRC patients [26].…”

“…Hayashi et al demonstrated that an early increase in the serum VEGF-A concentration after the initial decrease is a potential predictive marker of poor tumor response in the second-line FOLFIRI plus bevacizumab for metastatic CRC patients [26]. However, a different treatment-line setting and a blood collection point should be discussed, i.e.…”