Prediction of the treatment response in ovarian cancer: a ctDNA approach

Sharbatoghli, Mina; Vafaei, Somayeh; Es, Hamidreza Aboulkheyr; Asadi‐Lari, Mohsen; Totonchi, Mehdi; Madjd, Zahra

doi:10.1186/s13048-020-00729-1

Cited by 26 publications

(18 citation statements)

References 143 publications

(152 reference statements)

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“…A considerable number of studies, including ongoing clinical trials, examine ctDNA in relation to monitoring treatment response in EOC [ 12 , 33 ]; however, to date, no ctDNA-related test has been approved and evidence for using ctDNA to guide clinical decision making is weak [ 34 ]. In a study by Oikkonen et al, response to therapy using two or three consecutive ctDNA samples during treatment of EOC was examined, with the possibility of the rapid discovery of resistant cell populations and the early detection of recurrence [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Circulating Methylated Homeobox A9 DNA in Patients Undergoing Treatment for Recurrent Ovarian Cancer

Faaborg

Andersen

Waldstrøm

et al. 2022

Cancers

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Methylated Homeobox A9 circulating tumor DNA (meth-HOXA9) has been suggested as a blood-based biomarker in epithelial ovarian cancer (EOC), although its prognostic significance remains unproven. The aim of the present study was to investigate the prognostic impact of meth-HOXA9 in patients with recurrent EOC. DNA was purified from 4 mL plasma and, following bilsulfite conversion, meth-HOXA9 was analyzed using a methylation-specific droplet digital PCR. Detection of meth-HOXA9 was reported as a percentage of total DNA and as a binary variable (detectable and undetectable). Meth-HOXA9 status and its dynamics during palliative treatment were correlated with overall survival (OS) as the primary endpoint. At baseline, meth-HOXA9 was detected in 65.9% (83/126) of the patients. The median OS was 8.9 and 17.9 months in patients with detectable and undetectable meth-HOXA9 at baseline (hazard ratio: 2.04, p = 0.002), which remained significant in the multivariate analysis. Median OS in patients with an increase in meth-HOXA9 after one treatment cycle was 5.3 months compared to 33 months in patients with undetectable meth-HOXA9 (p < 0.001). Meth-HOXA9 was significantly related to poor survival and may serve as a prognostic marker in patients with recurrent EOC. The longitudinal monitoring of meth-HOXA9 is clinically feasible with the perspective of aiding clinical decision making.

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Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Circulating Methylated Homeobox A9 DNA in Patients Undergoing Treatment for Recurrent Ovarian Cancer

Faaborg

Andersen

Waldstrøm

et al. 2022

Cancers

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“…Organoids, i.e., 3D multicellular aggregates used to model human organ development, derived from primary tumors may be an especially useful platform for personalized medicine as genomic alterations are thought to be recapitulated in the organoid cultures [ 140 ]. Such genomic information can guide treatment [ 139 , 141 , 142 ]. Treatments can be further personalized by combining chemotherapies with immunotherapy treatments based on the tumor biology and the characteristics of the tumor microenvironment [ 143 ].…”

Section: Discussionmentioning

confidence: 99%

Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer

Levit

Tang

2021

Nanomaterials

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Treatment of ovarian cancer is challenging due to late stage diagnosis, acquired drug resistance mechanisms, and systemic toxicity of chemotherapeutic agents. Combination chemotherapy has the potential to enhance treatment efficacy by activation of multiple downstream pathways to overcome drug resistance and reducing required dosages. Sequence of delivery and the dosing schedule can further enhance treatment efficacy. Formulation of drug combinations into nanoparticles can further enhance treatment efficacy. Due to their versatility, polymer-based nanoparticles are an especially promising tool for clinical translation of combination therapies with tunable dosing schedules. We review polymer nanoparticle (e.g., micelles, dendrimers, and lipid nanoparticles) carriers of drug combinations formulated to treat ovarian cancer. In particular, the focus on this review is combinations of platinum and taxane agents (commonly used first line treatments for ovarian cancer) combined with other small molecule therapeutic agents. In vitro and in vivo drug potency are discussed with a focus on quantifiable synergistic effects. The effect of drug sequence and dosing schedule is examined. Computational approaches as a tool to predict synergistic drug combinations and dosing schedules as a tool for future nanoparticle design are also briefly discussed.

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“…Recently, advances in therapeutic monitoring in EOC have been made with circulating tumor DNA (ctDNA) providing important evidence about its utility in determining outcome and individualizing cancer therapy in patients with EOC [65][66][67]; on the contrary, the role of circulating miRNAs in EOC clinical monitoring needs to be further investigated in order to obtain a larger concordance between the results from independent investigators. Of note, we should bear in mind that ctDNA represents a sort of barcode originating directly from the tumor, but "liquid" miRNAs are not derived uniquely from the cancerous mass.…”

Section: Discussionmentioning

confidence: 99%

Role of Circulating miRNAs in Therapeutic Response in Epithelial Ovarian Cancer: A Systematic Revision

et al. 2021

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Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification of most advanced primary and relapsed disease and correlates with disease burden; however, as well highlighted in the literature, CA-125 often lacks sensitivity and specificity, and is not helpful in monitoring chemotherapeutic response or in predicting the risk of relapse. Given that, the identification of novel biomarkers able to foster more precise medical approaches and the personalization of patient management represents an unmet clinical requirement. In this context, circulating miRNAs may represent an interesting opportunity as they can be easily detected in all biological fluids. This is particularly relevant when looking for non-invasive approaches that can be repeated over time, with no pain and stress for the oncological patient. Given that, the present review aims to describe the circulating miRNAs currently identified as associated with therapeutic treatments in OC and presents a complete overview of the available evidence.

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Prediction of the treatment response in ovarian cancer: a ctDNA approach

Cited by 26 publications

References 143 publications

Prognostic Impact of Circulating Methylated Homeobox A9 DNA in Patients Undergoing Treatment for Recurrent Ovarian Cancer

Prognostic Impact of Circulating Methylated Homeobox A9 DNA in Patients Undergoing Treatment for Recurrent Ovarian Cancer

Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer

Role of Circulating miRNAs in Therapeutic Response in Epithelial Ovarian Cancer: A Systematic Revision

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