Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09-01) trial

Pineda, Estela; Salud, Antonieta; Vila-Navarro, Elena; Safont, M.J.; Llorente, B.; Aparicio, Jorge; Vera, Ruth; Escudero, P.; Casado, Enrique; Bosch, C.; Bohn, Uriel; Perez-Carrion, R.; Carmona, Alberto; Ayuso, Juan Ramón; Ripollés, Tomás; Bouzas, Rosa; Gironella, Meritxell; García-Albéniz, Xabier; Feliú, Jaime; Maurel, Joan

doi:10.1177/1010428317705509

Cited by 11 publications

(3 citation statements)

References 16 publications

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“…In contrast, VEGF-A was decreased, and both PlGF and VEGF-D were significantly increased at progression in the BEV group. The dynamics in VEGF-A, VEGF-D, and PlGF after BEV administration, regardless of the primary organ, have been reported, [32][33][34] and we found consistent results in our analysis. Although angiogenesis inhibitors, such as BEV, RAM, and AFL, are key drugs used in 2L, no clear selection criteria are available.…”

Section: Median (Pgsupporting

confidence: 91%

Role of plasma angiogenesis factors in the efficacy of first‐line chemotherapy combined with biologics in RAS wild‐type metastatic colorectal cancer: Results from the GI‐SCREEN CRC‐Ukit study

Yuki,

Yamazaki,

Sunakawa

et al. 2023

Cancer Medicine

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BackgroundSeveral biomarkers have been established for metastatic colorectal cancer (mCRC). We investigated whether plasma angiogenesis factors could predict the efficacy of biologics combined with chemotherapy in first‐line (1L) treatment in patients with RAS wild‐type mCRC and the dynamics of plasma angiogenesis factors at progression during 1L treatment.MethodsIn this multicenter prospective observational study, serial plasma samples were prospectively collected at pretreatment and progression stages; 17 plasma angiogenesis factors were analyzed using the multiplex assay with Luminex® technology. Interactions between the pretreatment measurements and treatment groups on progression‐free survival (PFS) and overall survival (OS) in patients with RAS wild‐type were assessed using the propensity‐score weighted Cox proportional hazards model.ResultsFrom February 2018 to September 2020, 202 patients were enrolled in the 1L cohort; 133 patients had RAS wild‐type (chemotherapy plus bevacizumab [BEV group, n = 33] and plus anti‐epidermal growth factor receptor monoclonal antibodies [aEGFR group, n = 100]). A trend of strong interaction on PFS was observed for interleukin‐8 (IL‐8) (p = 0.0752) and soluble vascular cell adhesion molecule‐1 (sVCAM‐1) (p = 0.0156). Regarding OS, IL‐8 (p = 0.0283), soluble vascular endothelial growth factor‐receptor‐1 (sVEGFR‐1) (p = 0.0777) and sVCAM‐1 (p = 0.0011) tended to differentiate the treatment effect. In 112 patients, plasma samples were evaluable for dynamic analysis (57 and 55 from the BEV and aEGFR groups, respectively). In the BEV group, six factors significantly increased during progression, whereas two decreased. In the aEGFR group, three factors significantly increased, and six decreased.ConclusionPretreatment plasma IL‐8 and sVCAM‐1 levels could be predictive biomarkers to distinguish BEV and anti‐EGFR mAbs when combined with chemotherapy in the 1L treatment of RAS wild‐type mCRC. Several plasma angiogenesis factors showed significant change at progression in 1L chemotherapy plus biologics for RAS wild‐type mCRC, which are potential biomarkers for selecting an optimal angiogenesis inhibitor in second‐line treatment.

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Section: Median (Pgsupporting

confidence: 91%

Role of plasma angiogenesis factors in the efficacy of first‐line chemotherapy combined with biologics in RAS wild‐type metastatic colorectal cancer: Results from the GI‐SCREEN CRC‐Ukit study

Yuki,

Yamazaki,

Sunakawa

et al. 2023

Cancer Medicine

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“…During Bevacizumab exposure, VEGF-A is decreased, but increased levels of VEGFR1 result in drug resistance. Decreased hepatocyte growth factor (HGF) levels are observed during acquired resistance, suggesting the potential implementation of strategies to counter HGF-ligand inhibition[ 41 ]. Findings by Carbone et al[ 42 ] propose a role for the transcription factor HOXB9 as one of the key mechanisms of anti-VEGF resistance.…”

Section: Introductionmentioning

confidence: 99%

Drug resistance and new therapies in colorectal cancer

Jeught

et al. 2018

WJG

456

220

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Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.

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“…During bevacizumab exposure, VEGF-A is decreased, instead of increased levels of vascular endothelial growth factor receptor 1 (VEGFR1) which result in drug resistance. Hepatocyte growth factor (HGF)-ligand inhibition and silencing HOXB9 is expected to be a promising approach to regulate this resistance[ 29 , 30 ].…”

Section: Targeting Angiogenesismentioning

confidence: 99%

Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges

Matsuoka¹,

Yashiro²

2021

WJGO

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Gastrointestinal (GI) cancer remains the deadliest cancer in the world. The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery, and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI cancer. There is well-established evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies, which should routinely be incorporated into treatment strategies for GI cancer. Other potential therapeutic targets involve the PI3K/AKT pathway, tumor growth factor-β pathway, mesenchymal-epithelial transition pathway, WNT pathway, poly (ADP-ribose) polymerase, and immune checkpoints. Many clinical trials assessing the agents of targeted therapy are underway and have presented promising and thought-provoking results. With the development of molecular biology techniques, we can identify more targetable molecular alterations in larger patient populations with GI cancer. Targeting these molecules will allow us to reach the goal of precision medicine and improve the outcomes of patients with GI cancer.

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Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09-01) trial

Cited by 11 publications

References 16 publications

Role of plasma angiogenesis factors in the efficacy of first‐line chemotherapy combined with biologics in RAS wild‐type metastatic colorectal cancer: Results from the GI‐SCREEN CRC‐Ukit study

Role of plasma angiogenesis factors in the efficacy of first‐line chemotherapy combined with biologics in RAS wild‐type metastatic colorectal cancer: Results from the GI‐SCREEN CRC‐Ukit study

Drug resistance and new therapies in colorectal cancer

Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges

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