Predictive biomarker candidates to delineate efficacy of antiangiogenic treatment in renal cell carcinoma

Romero-Laorden, Nuria; Doger, Bernard; Hernández, Maurenis; Hernández, Carolina; Rodriguez-Moreno, Juan Francisco; García-Donás, Jesús

doi:10.1007/s12094-015-1332-9

Cited by 8 publications

(6 citation statements)

References 78 publications

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“…The expression of ATAD2 in various malignant tumors is significantly higher than that in normal tissues (9), and ATAD2 has been used to evaluate the clinical prognosis of various cancers, such as lung cancer (10, 11), breast cancer (11), hepatocellular carcinoma (12), ovarian cancer (13), endometrial cancer (14) and gastric cancer (15), which are consistent with the results of ATAD2 expression in our study. Notably, we found that the expression levels of ATAD2 were up-regulated in LUAD tissues and cell lines compared to normal lung tissues and cell lines, respectively (Fig.…”

Section: Discussionsupporting

confidence: 89%

ATAD2 expression increases [18F]Fluorodeoxyglucose uptake value in lung adenocarcinoma via AKT-GLUT1/HK2 pathway

Diao

et al. 2019

BMB Rep.

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[18F]Fluorodeoxyglucose (FDG) PET/CT imaging has been widely used in the diagnosis of malignant tumors. ATPase family AAA domain-containing protein 2 (ATAD2) plays important roles in tumor growth, invasion and metastasis. However, the relationship between [18F]FDG accumulation and ATAD2 expression remains largely unknown. This study aimed to investigate the correlation between ATAD2 expression and [18F]FDG uptake in lung adenocarcinoma (LUAD), and elucidate its underlying molecular mechanisms. The results showed that ATAD2 expression was positively correlated with maximum standardized uptake value (SUV max ), total lesion glycolysis (TLG), glucose transporter type 1 (GLUT1) expression and hexokinase2 (HK2) expression in LUAD tissues. In addition, ATAD2 knockdown significantly inhibited the proliferation, tumorigenicity, migration, [18F]FDG uptake and lactate production of LUAD cells, while, ATAD2 overexpression exhibited the opposite effects. Furthermore, ATAD2 modulated the glycometabolism of LUAD via AKT-GLUT1/HK2 pathway, as assessed using LY294002 (an inhibitor of PI3K/AKT pathway). In summary, to explore the correlation between ATAD2 expression and glycometabolism is expected to bring good news for anti-energy metabolism therapy of cancers.

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Section: Discussionsupporting

confidence: 89%

ATAD2 expression increases [18F]Fluorodeoxyglucose uptake value in lung adenocarcinoma via AKT-GLUT1/HK2 pathway

Diao

et al. 2019

BMB Rep.

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“…For the exploration of gene mutations, a single-arm, phase II study of apatinib in refractory metastatic colorectal cancer has analyzed a panel of 1,021 cancer-related genes by ctDNA, but has not found any positive results associated with PFS or OS 56 . One possible explanation is that by blocking VEGF signal transduction, antiangiogenic therapies act not only on tumor cells but also on the microenvironment 57 , 58 , thus making identification of a biomarker in ctDNA difficult. Our investigation revealed an association between gene alterations in ctDNA at baseline and outcomes during antiangiogenic-based therapy, thus demonstrating that clinical outcomes depend on somatic variants, in terms of both mutation burden and frequency.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA

Zhu

Yuan

et al. 2021

Cancer Biol. Med.

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Objective: Apatinib is an oral TKI targeting VEGFR-2. Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated mBC. Oral vinorelbine also holds promise as a treatment of choice in patients with mBC. This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated mBC. In addition, we detected gene variants in ctDNA to explore the therapeutic implications. Methods: This study enrolled patients with HER2-negative mBC who were pretreated with anthracycline/taxanes. Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m 2 on days 1, 8, and 15 of every cycle (3 weeks). The primary endpoint was PFS. The secondary endpoints were ORR, CBR, OS, and safety. Patients eligible for ctDNA detection were evaluated before and during treatment. Results: Forty patients were enrolled. The median PFS was 5.2 months (95% CI, 3.4-7.0 months), and the median OS was 17.4 months (95% CI, 8.0-27.0 months). The ORR was 17.1% (6/35), and the CBR was 45.7% (16/35). The most common AEs included gastrointestinal reaction, myelosuppression, and hypertension. In 20 patients, ctDNA was detected at baseline and during treatment. A significant difference was found in PFS for undetected vs. detected baseline ctDNA (13.9 months vs. 3.6 months, P = 0.018). Conclusions: All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2negative mBC, with acceptable and manageable toxicity profiles. Patients with no gene variant detected and lower variant allele frequencies in ctDNA at baseline showed longer PFS.

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“…Predictive factors, especially those related to the physiopathologic process of mRCC, could be helpful in guiding therapy for these patients. To date, plasma predictive factors have not been clearly established (18). Another point to address is the evaluation of tumor response classically based on the RECIST criteria (e.g., a decrease in the size of tumor lesions).…”

Section: Introductionmentioning

confidence: 99%

Sunitinib Prior to Planned Nephrectomy in Metastatic Renal Cell Carcinoma: Angiogenesis Biomarkers Predict Clinical Outcome in the Prospective Phase II PREINSUT Trial

Mauge

Méjean

Fournier

et al. 2018

Clinical Cancer Research

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The PREINSUT study characterized factors predictive of response to sunitinib given before planned nephrectomy in patients with metastatic renal cell carcinoma (mRCC). This French multicenter, prospective, open-label, phase II trial (NCT00930345) included treatment-naïve patients with clear-cell mRCC. Patients received two cycles of sunitinib before nephrectomy. The primary objective was to evaluate the potential of circulating angiogenesis-related biomarkers measured before and on treatment for identifying responders based on primary renal tumor (PRT) size change. Secondary objectives were to evaluate the ability of biomarkers to predict progression-free survival (PFS) and overall survival (OS). Thirty-two patients were enrolled. The median PFS was 4.5 months, and the median OS was 12.4 months. OS was significantly longer in responding patients (28.8 vs. 11.1 months; = 0.03). Of 27 patients evaluable for PRT response, nine (33.3%) had a ≥10% decrease in PRT size. Baseline biomarkers significantly associated with outcome were endothelial progenitor cells (PRT response); vascular endothelial growth factor (VEGF)-A, stromal cell-derived factor-1 (SDF-1), soluble VEGF receptors (sVEGFR)1 and 2 (PFS); and SDF-1 and sVEGFR1 (OS). During treatment, changes in biomarkers associated with outcome were SDF-1 and platelet-derived growth factor (PDGF)-BB (PRT response), sVEGFR2 (PFS), and SDF-1 and sVEGFR1 (OS). There was no correlation between plasma sunitinib or its active metabolite steady-state trough concentrations and clinical outcome. Angiogenesis-related parameters that could reflect hypoxia seem to be associated with worse outcome in mRCC. As blood biomarkers are not subjected to tumor heterogeneity and allow longitudinal follow-up, circulating angiogenesis profile has a promising place in antiangiogenic therapy guidance. .

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Predictive biomarker candidates to delineate efficacy of antiangiogenic treatment in renal cell carcinoma

Cited by 8 publications

References 78 publications

ATAD2 expression increases [18F]Fluorodeoxyglucose uptake value in lung adenocarcinoma via AKT-GLUT1/HK2 pathway

ATAD2 expression increases [18F]Fluorodeoxyglucose uptake value in lung adenocarcinoma via AKT-GLUT1/HK2 pathway

Phase II study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA

Sunitinib Prior to Planned Nephrectomy in Metastatic Renal Cell Carcinoma: Angiogenesis Biomarkers Predict Clinical Outcome in the Prospective Phase II PREINSUT Trial

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