A systematic literature review assessing if genetic biomarkers are predictors for platinum-based chemotherapy response in ovarian cancer patients

Phillips-Chavez, Caitlin; Watson, Michael; Coward, Jermaine; Schloss, Janet

doi:10.1007/s00228-020-02874-4

Cited by 7 publications

(6 citation statements)

References 71 publications

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“…Chemotherapy resistance is the main clinical obstacle in the treatment of ovarian cance. Previous prognostic indicators such as age, stage, and histological type are not enough to predict the efficacy of conventional chemotherapy [ 30 ]. Therefore, new biomarkers to predict chemotherapy resistance and treatment strategies to overcome resistance are needed.…”

Section: Discussionmentioning

confidence: 99%

LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer

et al. 2021

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Objective LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resistance and prognosis of ovarian cancer was confirmed in experiments. Methods Multiple databases have performed the bioinformatics analysis of methylation and transcription factor binding site (TFBS) on the promoter region of LAMA3 gene. Pyrosequencing detected the methylation of LAMA3. QRT-PCR and immunohistochemistry detected the expression of LAMA3. Real Time Cell Analyzer (RTCA) detects changes in cell proliferation, migration and invasion ability. Flow cytometry was used to detect apoptosis. Results CPG islands of 176 bp, 134 bp, 125 bp and 531 bp were predicted in the promoter region of LAMA3 gene. The 4 prediction results are basically overlapped. 7 transcription factor binding sites were predicted, and the one with the highest score was on the predicted CpG island located in the proximal promoter region. LAMA3 hypermethylation and low expression are both associated with chemotherapy resistance and poor prognosis in ovarian cancer. LAMA3 methylation was negatively correlated with expression. After upregulation of LAMA3, the proliferation ability of chemoresistant ovarian cancer cell decreased, while the ability of apoptosis, invasion and migration increased. Conclusion LAMA3 hypermethylation is associated with chemotherapy resistance and poor prognosis. As a typical CpG island gene, LAMA3(cg20937934) and LAMA3(cg13270625) hypermethylation is negatively correlated with low expression. LAMA3 promotes the invasion, migration and apoptosis of SKOV3DDP. In the future, the mechanism of LAMA3 methylation in ovarian cancer will need to be further studied.

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Section: Discussionmentioning

confidence: 99%

LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer

et al. 2021

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“…The prognosis of patients with advanced ovarian cancer is poor. Most patients succumb to disease progression [6], and will die of platinum-resistant disease, primarily due to the accumulation of chemoresistant CSCs in the peritoneal cavity [12][13][14]. The ability to target chemoresistant CSCs has been a major barrier to the development of novel therapies for patients with advanced disease.…”

Section: Discussionmentioning

confidence: 99%

“…The standard of care for advanced ovarian cancer comprises primary debulking followed by combination chemotherapy using paclitaxel and carboplatin [4,5]. Despite an initial clinical response, approximately 80% of patients experience disease recurrence within 2 years [6]. Treatment approaches vary, and include the use of neoadjuvant chemotherapy prior to cytoreduction, use of a variety of different chemotherapy dosing strategies (e.g., weekly paclitaxel with or without weekly carboplatin), and the addition of antiangiogenic drugs (e.g., IV bevacizumab) into first-line treatment, followed by maintenance [7].…”

Section: Introductionmentioning

confidence: 99%

Maximum Tolerated Dose and Anti-Tumor Activity of Intraperitoneal Cantrixil (TRX-E-002-1) in Patients with Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer: Phase I Study Results

Coward

Barve

Kichenadasse

et al. 2021

Cancers

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Survival outcomes in ovarian cancer are poor. The aims of this Phase I progressive design study (NCT02903771) were to evaluate the maximum tolerated dose (MTD), tolerability, and antitumor activity of Cantrixil—a novel third-generation benzopyran molecule—in patients (n = 25) with advanced, recurrent/persistent epithelial ovarian, primary peritoneal, or fallopian tube cancer. All had completed ≥ 2 prior regimens; 3 (12%) had platinum-refractory disease, and 17 (68%) had platinum-resistant disease. Following intraperitoneal (IP) port placement, patients received weekly IP Cantrixil in 3-week cycles as monotherapy (Cycles 1–2), and then in combination with intravenous (IV) chemotherapy (Cycles 3–8). Part A (dose escalation) enrolled 11 patients in 6 dose-level cohorts. An MTD of 5 mg/kg was established with dose-limiting toxicity of ileus. Most treatment-related adverse events were gastrointestinal. Across Parts A and B (dose expansion), 16 (64%) patients received ≥ 1 3-week Cantrixil cycle, and had ≥ 1 post-baseline efficacy measurement available. The results show promising anti-tumor activity in monotherapy (stable disease rate of 56%) and in combination with IV chemotherapy (objective response rate of 19%, disease control rate of 56%, and median progression-free survival of 13.1 weeks). The molecular target and mechanism of action of Cantrixil are yet to be confirmed. Preliminary analysis of stem cell markers suggests that IP Cantrixil might induce ovarian cancer stem cell death and sensitize cells to standard chemotherapy, warranting further evaluation.

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“…Furthermore, the diagnostic tools of ovarian cancer may not be able to detect early stages of the disease, distinguish between disease stages and metastatic potential, or are not routinely performed. Genetic profiling of biopsies, circulating tumor cells, or bodily fluids are used to screen for specific mutations or secreted proteins; however, the genetic or protein markers are often only applicable to a subset of patients due to the inherent heterogeneity of tumors ( Phillips-Chavez et al. , 2020 ) or do not include epigenetic changes, miRNA, circular RNA, exosomes, or stimuli from other cells in the tumor microenvironment that all can contribute to disease progression ( Tran et al.…”

Section: Introductionmentioning

confidence: 99%

Quantitative biophysical metrics for rapid evaluation of ovarian cancer metastatic potential

Mukherjee

Zhang

Ladner

et al. 2022

MBoC

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Ovarian cancer is routinely diagnosed long after the disease has metastasized through the fibrous sub-mesothelium. Despite extensive research in the field linking ovarian cancer progression to increasingly poor prognosis, there are currently no validated cellular markers or hallmarks of ovarian cancer that can predict metastatic potential. To discern disease progression across a syngeneic mouse ovarian cancer progression model, here, we fabricated extracellular-matrix mimicking suspended fiber networks: crosshatches of mismatch diameters for studying protrusion dynamics, aligned same diameter networks of varying inter-fiber spacing for studying migration, and aligned nanonets for measuring cell forces. We found that migration correlated with disease, while force-disease biphasic relationship exhibited f-actin stress-fiber network dependence. However, unique to suspended fibers, coiling occurring at tips of protrusions and not the length or breadth of protrusions displayed strongest correlation with metastatic potential. To confirm that our findings were more broadly applicable beyond the mouse model, we repeated our studies in human ovarian cancer cell lines and found that the biophysical trends were consistent with our mouse model results. Altogether, we report complementary high throughput and high content biophysical metrics capable of identifying ovarian cancer metastatic potential on time scale of hours. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

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A systematic literature review assessing if genetic biomarkers are predictors for platinum-based chemotherapy response in ovarian cancer patients

Cited by 7 publications

References 71 publications

LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer

LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer

Maximum Tolerated Dose and Anti-Tumor Activity of Intraperitoneal Cantrixil (TRX-E-002-1) in Patients with Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer: Phase I Study Results

Quantitative biophysical metrics for rapid evaluation of ovarian cancer metastatic potential

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