Ovarian cancer – from biology to clinic

Kujawa, Katarzyna Aleksandra; Lisowska, Katarzyna

doi:10.5604/17322693.1184451

Cited by 91 publications

(39 citation statements)

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“…A significant proportion of ovarian cancer patients are diagnosed at the advanced stage of the disease and have a poor response to current chemotherapeutic interventions ( 2 , 33 , 34 ). It is therefore considered essential to not only to develop more effective and less toxic therapeutic agents for the management of such patients, but also to identify more reliable biomarkers for earlier diagnosis, predicting the response, and guiding the treatment ( 2 , 3 , 6 , 8 , 16 , 35 , 36 ). As noted earlier, the aberrant activation of the cell signaling pathways by the epidermal growth factor receptor members have been reported in a wide range of human cancers including ovarian cancer, and this has been associated with a poorer prognosis in many such patients ( 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…As a result, the 5-year survival rates for ovarian cancer patients who are diagnosed at stages I/II and III/IV is 90 and 20–40% respectively ( 2 , 5 ). This highlights the urgent need for the development of novel and more effective therapeutic agents with different mechanisms of action, and the identification of biomarkers for use in the early detection of such cancers and for the selection of relevant patient populations who may benefit from such therapeutic interventions ( 3 , 6 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

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Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

Puvanenthiran

Essapen

Seddon

et al. 2016

International Journal of Oncology

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Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer stem cell (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), and HER family members and response to treatment with these agents. The sensitivity of 10 ovarian tumour cell lines to the treatment with various forms of HER TKIs (gefitinib, erlotinib, lapatinib, sapitinib, afatinib, canertinib, neratinib), as well as other TKIs (dasatinib, imatinib, NVP-AEW541, crizotinib) and cytotoxic agents (paclitaxel, cisplatin and doxorubicin), as single agents or in combination, was determined by SRB assay. The effect on these agents on the cell cycle distribution, and downstream signaling molecules and tumour migration were determined using flow cytometry, western blotting, and the IncuCyte Clear View cell migration assay respectively. Of the HER inhibitors, the irreversible pan-TKIs (canertinib, neratinib and afatinib) were the most effective TKIs for inhibiting the growth of all ovarian cancer cells, and for blocking the phosphorylation of EGFR, HER-2, AKT and MAPK in SKOV3 cells. Interestingly, while the majority of cancer cells were highly sensitive to treatment with dasatinib, they were relatively resistant to treatment with imatinib (i.e., IC50 >10 μM). Of the cytotoxic agents, paclitaxel was the most effective for inhibiting the growth of OCCLs, and of various combinations of these drugs, only treatment with a combination of NVP-AEW541 and paclitaxel produced a synergistic or additive anti-proliferative effect in all three cell lines examined (i.e., SKOV3, Caov3, ES2). Finally, of the TKIs, only treatment with afatinib, neratinib and dasatinib were able to reduce the migration of HER-2 overexpressing SKOV3 cells. We did not find any significant association between the expression of putative ovarian CSC marker, HER family members, c-MET, ALK, and IGF-IR and the response to the irreversible HER TKIs. Our results support the need for further investigations of the therapeutic potential of these irreversible HER family blockers in ovarian cancer, and the therapeutic potential of dasatinib when used in combination with the inhibitors of the HER family members in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

Puvanenthiran

Essapen

Seddon

et al. 2016

International Journal of Oncology

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“…Characteristics of patients and tumor samples. 1 Residual tumor size: R0 = 0 cm, R1 < 0.5 cm, R2-between 0.5 cm and 2 cm, R2 ≥ 2 cm; 2 Chemotherapy (CHT) response, described as clinical status of the patient after first-line treatment: CR-complete response, PR-partial response, NC-no change, P-progression; RECIST-Response Evaluation Criteria in Solid Tumors; 3 Tumors were classified as highly sensitive when disease free survival (DFS) > 732 days, moderately sensitive when 732 days > DFS > 180 days, and resistant when DFS < 180 days *-classification criteria given by Barber [26].…”

Section: Clinical Samples Used For Survival Analysismentioning

confidence: 99%

“…Ovarian cancer is a highly heterogeneous disease, and this phenomenon is probably due to the distinct cellular origin of its individual histological types. Recent findings suggest that clear cell and endometrioid ovarian cancers originate from endometriosis, while serous ovarian cancers may originate either from the ovarian surface or fallopian tube epithelium [1][2][3]. The heterogeneity of ovarian cancer is also legible at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Kujawa

Zembala‐Nożyńska

Cortez

et al. 2020

Cells

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Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan–Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan–Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02–4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian–epithelial origin of the tumor.

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“…Ovarian cancer is the largest cause of death among gynaecological cancers. This disease is initially asymptomatic and, therefore, is usually detected in advanced stages when complete recovery is most often impossible [25]. Research on the biology of this cancer has been ongoing for many years Then, for OPG and the CA 125 antigen, ROC curves were drawn, illustrated in Figure 5, and the values of the areas under them, the AUCs, were determined.…”

Section: Discussionmentioning

confidence: 99%

Changes in the Concentration of Markers Participating in the Regulation of the Apoptosis Receptor Pathway Involving Soluble Tumour Necrosis Factor Ligand Inducing Apoptosis (sTRAIL) and Osteoprotegerin (OPG) in the Serum of Women with Ovarian Cancer—Participation in Pathogenesis or a Possible Clinical Use?

Mielczarek‐Palacz

Kondera-Anasz

Smycz‐Kubańska

2020

Cells

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Due to the ability to selectively induce apoptosis in cancer cells, the most interesting target for clinical research is the tumour necrosis factor ligand inducing apoptosis (TRAIL), which binds specific receptors, including osteoprotegerin (OPG). The aim of the study was to analyse the concentration of soluble TRAIL (sTRAIL) and OPG in the serum of women with serous or mucinous ovarian cancer, taking into account different levels of cancer histological differentiation. The group included 97 women with the diagnosed Cystadenocarcinoma papillare serosum IIIc and Cystadenocarcinoma mucinosum IIIc. Concentrations of parameters were measured by ELISA. Analysis of the obtained results showed a statistically significantly higher concentration of sTRAIL and OPG in the serum of women with ovarian serous and mucinous cancer compared to the control group (p < 0.0001). Statistical significance was found between sTRAIL and OPG concentration in G1 and G3 serous cancer (p < 0.01) and in OPG mucinous cancer between G1 and G3 (p < 0.01) and G2 and G3 (p < 0.01). An important role in the pathogenesis of ovarian cancer is played by disorders of the apoptosis process involving the sTRAIL/OPG system, which are associated with the histological type and the degree of histological differentiation of the tumour. Determining the concentration of tested parameters in combination with other markers may be useful in the future in the diagnosis of ovarian cancer, but that requires further research.

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Ovarian cancer – from biology to clinic

Cited by 91 publications

References 0 publications

Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

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