Dynamic Angiogenic Switch as Predictor of Response to Chemotherapy-Bevacizumab in Patients With Metastatic Colorectal Cancer

Cubillo, Antonio; Alvarez-Gallego, Rafael; Muñoz, Manuel; Pond, Gregory R.; Perea, Sofía; Sánchez, Gema María Varo; Martín, M. Segura; Rodríguez-Pascual, Jesús; Garralda, Elena; Vega, Estela; Vicente, Emilio; Quijano, Yolanda; Muñoz, César; Ugidos, Lisardo; Toledo, Rodrigo A.; Hidalgo, Manuel

doi:10.1097/coc.0000000000000474

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…PLGF was observed in tumor cells and vascular endothelial cells in hypoxic GBM, indicating that the TME under hypoxic conditions is also a source of PLGF [ 21 ]. PLGF elevation is significant during Bev therapy response in patients with metastatic colorectal cancer [ 31 ] and GBM [ 10 ], making it a reliable as a predictive biomarker in clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment

Ezaki,

Tanaka,

Tamura

et al. 2024

Brain Tumor Pathol

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Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.

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Section: Discussionmentioning

confidence: 99%

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment

Ezaki,

Tanaka,

Tamura

et al. 2024

Brain Tumor Pathol

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“…Evidence highlighting the critical role played by angiogenic factors in immune regulation and CRC progression is increasing [64][65][66]. Angiogenic factors excreted by CRC cells are known to stimulate endothelial cells to regulate angiogenic switches during CRC development [67]. In addition, angiogenic factors contribute to a pattern of impaired immune activation (immunosuppression) by activating suppressive immune cells or inhibiting immune effector cells, which can in turn stimulate angiogenesis and tumor progression [68,69].…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a novel angiogenesis pattern to predict prognosis and immunotherapy efficacy in colorectal cancer

Li,

Liu,

Guo

et al. 2023

Aging

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Background: Evidence suggests that the tumor microenvironment (TME) affects the tumor active response to immunotherapy. Tumor angiogenesis is closely related to the TME. Nonetheless, the effects of angiogenesis on the TME of colorectal cancer (CRC) remain unknown. Methods: We comprehensively assessed the angiogenesis patterns in CRC based on 36 angiogenesis-related genes (ARGs). Subsequently, we evaluated the prognostic values and therapeutic sensitivities of angiogenesis patterns using multiple methods. We then performed the machine learning algorithm and functional experiments to identify the prognostic key ARGs. Ultimately, the regulation of gut microbiota on the expression of ARGs was further investigated by using whole genome sequencing. Results: Two angiogenesis clusters were identified and angiogenesis cluster B was characterized by increased stromal and immunity activation with unfavorable odds of survival. Further, an ARG_score including 9 ARGs to predict recurrence-free survival (RFS) was established and its predominant predictive ability was confirmed. The low ARG_score patients were characterized by a high mutation burden, high microsatellite instability, and immune activation with better prognosis. Moreover, patients with high KLK10 expression were associated with a hot tumor immune microenvironment, poorer immune checkpoint blocking treatment, and shorter survival. The in vitro experiments also indicated that Fusobacterium nucleatum ( F.n ) infection significantly induced KLK10 expression in CRC. Conclusions: The quantification of angiogenesis patterns could contribute to predict TME characteristics, prognosis, and individualized immunotherapy strategies. Furthermore, our findings suggest that F.n may influence CRC progression through ARGs, which could serve as a clinical biomarker and therapeutic target for F.n -infected CRC patients.

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“…PLGF was observed in tumor cells and vascular endothelial cells in hypoxic GBM, indicating that the TME under hypoxic conditions is also a source of PLGF [21]. PLGF elevation is signi cant as a predictor of Bev therapy response in patients with metastatic colorectal cancer [31] and GBM [10], making it a reliable biomarker for predicting clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment

Tanaka,

Tamura,

Yamamoto

et al. 2023

Preprint

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Purpose: Glioblastoma acquires resistance to Bevacizumab (Bev) treatment. Bev effects on angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood; therefore, we investigated changes in various angiogenic factors in glioblastoma under and after Bev therapy, including angiopoietin 1, angiopoietin 2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and Ephrin A2 (EFNA2). Methods: Fifty-four glioblastoma tissues were analyzed, including 28 specimens from 14 cases as ‘paired specimens from the same patient’ obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry was used to investigate angiogenic factor expression in tumor vessels and their association with recurrent MRI patterns. Results: PLGF expression was significantly higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractoryBev group. ANGPT2 and EFNA2 levels were higher in the refractory Bev group than in the naïveBev group (p = 0.047 and 0.028, respectively). Notably, PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe MRI patterns (p = 0.046). Conclusion: This is the first comparative study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived glioblastoma specimens. Alternative angiogenesis pathways may be concertedly involved in the resistance, which will inform optimization and development of novel therapeutics for improvedBevtherapy.

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Dynamic Angiogenic Switch as Predictor of Response to Chemotherapy-Bevacizumab in Patients With Metastatic Colorectal Cancer

Abstract: Chemotherapy plus Bevacizumab combination in mCRC patients results in dynamic changes in plasma cytokines, which is associated with better disease control and longer PFS. These new findings support continuing studying AS as a potential marker of angiogenesis inhibitor effectiveness.

Cited by 8 publications

References 19 publications

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment

Construction and validation of a novel angiogenesis pattern to predict prognosis and immunotherapy efficacy in colorectal cancer

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment

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