Antiangiogenic agents in gynecological cancer: State of art and perspectives of clinical research

Gadducci, Angiolo; Lanfredini, Nora; Sergiampietri, Claudia

doi:10.1016/j.critrevonc.2015.05.009

Cited by 25 publications

(14 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, comprehensive interrogation of protein phosphorylation identified multiple pathways with significantly increased phosphorylation in patients with poor clinical outcomes. Specifically, the observed activation of PDGFR pathways in a subset of patients with short overall survival could potentially stratify patients for selective enrollment in trials of anti-angiogenic therapy, which is particularly relevant to current controversies over the use of bevacuzimab as a first-line therapy in ovarian cancer (Gadducci et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

Zhang

Petyuk

et al. 2016

Cell

848

988

View full text Add to dashboard Cite

SUMMARY To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSC). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease such as how different copy number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, as well as the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

Zhang

Petyuk

et al. 2016

Cell

848

988

View full text Add to dashboard Cite

show abstract

“…Together with the observations at final analysis that OS and PFS remain significantly improved among those randomized to the arms administering bevacizumab, GOG 240 stands as a proof of concept of anti-angiogenesis therapy in this disease. 22 This in turn suggests that bevacizumab monotherapy deserves some consideration, particularly among patients intolerable to anti-neoplastic therapy despite several dose reductions ultimately requiring the peeling back of chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)

et al. 2017

View full text Add to dashboard Cite

Background On August 14, 2014, the United States Food and Drug Administration approved the anti-angiogenesis drug, bevacizumab, for women with advanced cervical cancer based on a 2012 interim analysis of 271 deaths on GOG protocol 240. We now report the planned protocol-specified final analysis of the primary objective, overall survival (OS). Methods A phase III randomized trial using a 2×2 factorial design was conducted to determine whether intravenous chemotherapy [(cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2) or (topotecan 0.75 mg/m2 days 1–3 plus paclitaxel 175 mg/m2)] with or without bevacizumab (15 mg/kg) improves OS in recurrent/persistent/metastatic cervical cancer. Patients were prospectively stratified by performance status, prior radiosensitizing platinum, and disease status. We estimated enrolling 450 patients with 346 deaths at final analysis to provide 90% power to detect a 30% reduction in risk of death. Findings On March 7, 2014, 348 deaths occurred among 452 patients. Regimens administering bevacizumab continued to demonstrate significant improvement in OS: 16.8 vs 13.3 mos (HR 0.77;95% CI 0.62–0.95;p=0.0068). Updated progression-free survival also favored bevacizumab (HR 0.68;95% CI 0.56–0.84;p=0.0002). Final OS among 20% (n=91) not treated with prior pelvic radiotherapy was 24.5 (bevacizumab) vs 16.8 mos (without bevacizumab). Fistula (any grade) occurred in 14.5% (n=32) receiving bevacizumab (all previously irradiated). Grade 3+ fistula developed in 5.9% (n=13) and did not result in surgical emergency, sepsis and/or death. Post-progression OS was not significantly different among those who did and did not receive bevacizumab (median 8.4 vs 7.1 mos: HR 0.32;95% CI 0.66–1.05;p=0.06). Interpretation The benefit conferred by incorporation of bevacizumab is sustained with extended follow-up as evidenced by the survival curves remaining separated. Following progression on bevacizumab, a negative rebound effect was not observed. This represents proof-of-concept of the efficacy and tolerability of anti-angiogenesis therapy in advanced cervical cancer. Funding National Cancer Institute (USA).

show abstract

“…Currently, chemotherapy is a treatment option for most types of ovarian cancer30. However, the effectiveness of chemotherapeutics can be limited by multiple tumour cells’ defence mechanisms31.…”

Section: Discussionmentioning

confidence: 99%

3′-hydroxy-3,4,5,4′-tetramethoxystilbene, the metabolite of resveratrol analogue DMU-212, inhibits ovarian cancer cell growth in vitro and in a mice xenograft model

Piotrowska‐Kempisty

Ruciński

Borys

et al. 2016

Sci Rep

View full text Add to dashboard Cite

In screening studies, the cytotoxic activity of four metabolites of resveratrol analogue 3,4,5,4′-tetramethoxystilbene (DMU-212) against A-2780 and SKOV-3 ovarian cancer cells was investigated. The most active metabolite, 3′-hydroxy-3,4,5,4′-tetramethoxystilbene (DMU-214), was chosen for further studies. The cytotoxicity of DMU-214 was shown to be higher than that of the parent compound, DMU-212, in both cell lines tested. Since DMU-212 was supposed to undergo metabolic activation through its conversion to DMU-214, an attempt was made to elucidate the mechanism of its anti-proliferative activity. We found that in SKOV-3 cells lacking p53, DMU-214 induced receptor-mediated apoptosis. In A-2780 cell line with expression of wild-type p53, DMU-214 modulated the expression pattern of p53-target genes driving intrinsic and extrinsic apoptosis pathways, as well as DNA repair and damage prevention. Regardless of the up-regulation of p48, p53R2, sestrins and Gaad45 genes involved in cancer cell DNA repair, we demonstrated the stronger anti-proliferative and pro-apoptotic effects of DMU-214 in A-2780 cells when compared to those in SKOV-3. Hence we verified DMU-214 activity in the xenograft model using SCID mice injected with A-2780 cells. The strong anti-proliferative activity of DMU-214 in the in vivo model allowed to suggest the tested compound as a potential therapeutic in ovarian cancer treatment.

show abstract

Antiangiogenic agents in gynecological cancer: State of art and perspectives of clinical research

Cited by 25 publications

References 117 publications

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)

3′-hydroxy-3,4,5,4′-tetramethoxystilbene, the metabolite of resveratrol analogue DMU-212, inhibits ovarian cancer cell growth in vitro and in a mice xenograft model

Contact Info

Product

Resources

About