Retrospective analysis of the role of cyclin E1 overexpression as a predictive marker for the efficacy of bevacizumab in platinum-sensitive recurrent ovarian cancer

Ribeiro, Adriana Regina G.; Salvadori, Marcella M.; Brot, Louise De; Bovolin, Graziele; Mantoan, Henrique; Ilelis, Felipe; Rezende, Mariana; Amaral, Nayra Soares do; Sanches, Solange Moraes; Maya, Joyce Maria Lisboa; Santos, Elizabeth Santana Dos; Pereira, Ronaldo; Castro, Fabrício de Souza; Lima, João Paulo da Nogueira Silveira; Guimarães, Andréa Paiva Gadêlha; Baiocchi, Glauco; Costa, Alexandre André Balieiro Anastácio da

doi:10.3332/ecancer.2021.1262

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…The protein expression of angiogenesis-related genes such as CCNE1, a disintegrin and metalloprotease 17 (ADAM17), mevalonate diphosphate decarboxylase (MVD), SMA_MVD, VEGFA, VEGFB, VGFR2, HIF-1α in tumor tissues was explored ( Fabbi et al, 2022 ). Only CCNE1 and VEGFB were proved to be predictive markers for the efficacy of bevacizumab ( Califano et al, 2021 ; Ribeiro et al, 2021 ). Circulating plasma or serum proteomic biomarkers are also assessed to their predictive value for PFS and OS.…”

Section: Biomarkers Of Anti-angiogenic Therapy In Ocmentioning

confidence: 99%

Anti-angiogenic therapy in ovarian cancer: Current understandings and prospects of precision medicine

et al. 2023

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Ovarian cancer (OC) remains the most fatal disease of gynecologic malignant tumors. Angiogenesis refers to the development of new vessels from pre-existing ones, which is responsible for supplying nutrients and removing metabolic waste. Although not yet completely understood, tumor vascularization is orchestrated by multiple secreted factors and signaling pathways. The most central proangiogenic signal, vascular endothelial growth factor (VEGF)/VEGFR signaling, is also the primary target of initial clinical anti-angiogenic effort. However, the efficiency of therapy has so far been modest due to the low response rate and rapidly emerging acquiring resistance. This review focused on the current understanding of the in-depth mechanisms of tumor angiogenesis, together with the newest reports of clinical trial outcomes and resistance mechanism of anti-angiogenic agents in OC. We also emphatically summarized and analyzed previously reported biomarkers and predictive models to describe the prospect of precision therapy of anti-angiogenic drugs in OC.

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Section: Biomarkers Of Anti-angiogenic Therapy In Ocmentioning

confidence: 99%

Anti-angiogenic therapy in ovarian cancer: Current understandings and prospects of precision medicine

et al. 2023

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“…In particular, PFI >12 months, the only factor for the longterm duration of BMT and improved PFS, has been considered as an important prognostic factor in PSR because longer PFI may have a greater chance to show response to chemotherapy (16,17). Previous studies reported that overexpression of cyclin and reduced levels of anti-angiogenic proteins were related to longer PFI in recurrent ovarian cancer (18,19). Thus, notable survival benefit has been shown in patients with PFI >12 months, compared to those with PFI <6 months or 6-12 months (20).…”

Section: Discussionmentioning

confidence: 99%

Platinum-free Interval May Predict Duration of Maintenance Bevacizumab and Survival in Platinum-sensitive Recurrent Ovarian Cancer

OH,

PARK,

LEE

et al. 2023

In Vivo

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Background/Aim: We investigated factors affecting the long-term duration of bevacizumab-based maintenance therapy (BMT) and survival in patients with the first platinum-sensitive recurrence of ovarian cancer (PSR). Patients and Methods: We included patients with the first PSR in two tertiary centers from January 2015 till August 2021. All patients received six cycles of paclitaxel, carboplatin, and bevacizumab followed by BMT. We collected data including age at recurrence, histologic types, the status of BRCA mutation, platinum-free interval (PFI), extent of secondary cytoreductive surgery (SCS), presence of extra-abdominal disease, numbers of recurred lesions, cycles of BMT, progression-free survival (PFS), and cancer-specific survival (CSS). The median cycles of . Results: A total 103 patients were included, who consisted of the short-term (<13 cycles; n=49; 47.6%) and long-term users of BMT (≥13 cycles; n=54; 52.4%). High-grade serous carcinoma (HGSC), PFI >12 months, and optimal cytoreduction during SCS were favorable factors for the long-term duration of BMT. Moreover, PFI >12 months and the long-term duration of BMT were factors for improved PFS, and HGSC and PFI >12 months were related to improved CSS. Conclusion: PFI >12 months may be associated with the long-term duration of BMT and improved survival in patients with the first PSR.

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“…Among other mechanisms of action, bevacizumab exposure may trigger HRD by inducing a hypoxic cellular state that can downregulate HR-related genes such as BRCA1/2 and RAD51 ( 117 ). In addition, the relative benefit of bevacizumab in EOC has been shown to increase as the disease becomes more platinum resistant ( 118 ). A retrospective analysis of 124 patients with platinum-sensitive recurrent ovarian cancer showed extended PFS with bevacizumab in patients with cyclin E1 overexpression (median 16.3 vs 7.1 months, P =0.010) ( 118 ).…”

Section: Treatment Options For Patients With Hrp Hgscmentioning

confidence: 99%

“…In addition, the relative benefit of bevacizumab in EOC has been shown to increase as the disease becomes more platinum resistant ( 118 ). A retrospective analysis of 124 patients with platinum-sensitive recurrent ovarian cancer showed extended PFS with bevacizumab in patients with cyclin E1 overexpression (median 16.3 vs 7.1 months, P =0.010) ( 118 ).…”

Section: Treatment Options For Patients With Hrp Hgscmentioning

confidence: 99%

Homologous recombination proficient subtypes of high-grade serous ovarian cancer: treatment options for a poor prognosis group

Stiegeler,

Garsed,

Au-Yeung

et al. 2024

Front. Oncol.

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Approximately 50% of tubo-ovarian high-grade serous carcinomas (HGSCs) have functional homologous recombination-mediated (HR) DNA repair, so-called HR-proficient tumors, which are often associated with primary platinum resistance (relapse within six months after completion of first-line therapy), minimal benefit from poly(ADP‐ribose) polymerase (PARP) inhibitors, and shorter survival. HR-proficient tumors comprise multiple molecular subtypes including cases with CCNE1 amplification, AKT2 amplification or CDK12 alteration, and are often characterized as “cold” tumors with fewer infiltrating lymphocytes and decreased expression of PD-1/PD-L1. Several new treatment approaches aim to manipulate these negative prognostic features and render HR-proficient tumors more susceptible to treatment. Alterations in multiple different molecules and pathways in the DNA damage response are driving new drug development to target HR-proficient cancer cells, such as inhibitors of the CDK or P13K/AKT pathways, as well as ATR inhibitors. Treatment combinations with chemotherapy or PARP inhibitors and agents targeting DNA replication stress have shown promising preclinical and clinical results. New approaches in immunotherapy are also being explored, including vaccines or antibody drug conjugates. Many approaches are still in the early stages of development and further clinical trials will determine their clinical relevance. There is a need to include HR-proficient tumors in ovarian cancer trials and to analyze them in a more targeted manner to provide further evidence for their specific therapy, as this will be crucial in improving the overall prognosis of HGSC and ovarian cancer in general.

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Retrospective analysis of the role of cyclin E1 overexpression as a predictive marker for the efficacy of bevacizumab in platinum-sensitive recurrent ovarian cancer

Cited by 4 publications

References 28 publications

Anti-angiogenic therapy in ovarian cancer: Current understandings and prospects of precision medicine

Anti-angiogenic therapy in ovarian cancer: Current understandings and prospects of precision medicine

Platinum-free Interval May Predict Duration of Maintenance Bevacizumab and Survival in Platinum-sensitive Recurrent Ovarian Cancer

Homologous recombination proficient subtypes of high-grade serous ovarian cancer: treatment options for a poor prognosis group

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