Epithelial ovarian cancer: Review article

Suchetha, S.

doi:10.1016/j.ctarc.2022.100629

Cited by 54 publications

(51 citation statements)

References 70 publications

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“…Despite the heterogeneous genomic landscape and the plethora of different histotypes/histologic subtypes of ovarian cancer, standard treatment is cytoreductive surgery and platinum-based chemotherapy [12,13]. Furthermore, even with optimized surgical strategies and the introduction of new therapies, such as poly ADP polymerase (PARP) inhibitors or antiangiogenic agents, the long-term survival in OC has not improved significantly during the last decades [14].…”

Section: Functional Precision Medicine (Fpm) Approaches Can Complemen...mentioning

confidence: 99%

The Drug Efficacy Testing in Ex Vivo 3D Cultures (DETECt) platform enables rapid identification of effective drugs and drug combinations for ovarian cancer patients

Seashore‐Ludlow

Åkerlund

Gudoitytė

et al. 2023

Preprint

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Most patients with advanced ovarian cancer (OC) relapse and progress despite systemic therapy, pointing to the need for improved and tailored therapy options. Functional precision medicine can help to identify effective therapies for individual patients in a clinically relevant timeframe. Here, we present a scalable functional precision medicine platform: DETECt (Drug Efficacy Testing in Ex vivo 3D Cultures), where the responses of primary patient cells to drugs and drug combinations are tested with live-cell imaging. We demonstrate the delivery of individual drug sensitivity profiles in 20 samples from 16 patients with ovarian cancer in both 2D and 3D culture formats, achieving over 90% success rate in providing actionable data six days after operation. All patients in this cohort received carboplatin as treatment and the ex vivo carboplatin drug response scores were significantly different between patients with a complete clinical response and those with a partial response or progression (p<0.05). In addition, carboplatin ex vivo response also predicted progression free interval (PFI) of patients (p<0.05). We find that the 3D culture format better retains proliferation and characteristics of the in vivo setting. Using the DETECt platform we evaluate 27 tailored combinations with results ready 10 days after operation. Notably, carboplatin and A-1331852 (Bcl-xL inhibitor) showed an additive effect in four of eight OC samples tested. Interestingly, afatinib treatment led to an increase of BIM and Bcl-xL expression in OC cells, which could be reversed by Bcl-xL inhibition, leading to increased cell death and synergy in 5/7 OC models. In conclusion, our 3D DETECt platform can rapidly define potential, clinically relevant data on efficacy of existing drugs in OC for precision medicine purposes, as well as provide insights on emerging drugs and drug combinations that warrant testing in clinical trials.

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Section: Functional Precision Medicine (Fpm) Approaches Can Complemen...mentioning

confidence: 99%

The Drug Efficacy Testing in Ex Vivo 3D Cultures (DETECt) platform enables rapid identification of effective drugs and drug combinations for ovarian cancer patients

Seashore‐Ludlow

Åkerlund

Gudoitytė

et al. 2023

Preprint

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“…The association between endometriosis and ovarian cancer was initially described in 1925 by Sampson, and then, it was confirmed by Scott in 1953, who observed that benign endometriosis may be present in proximity to ovarian cancer [ 2 ]. In particular, many studies confirm that the histotypes of epithelial ovarian cancer that are most closely related to endometriosis are endometrioid tumors and clear cell carcinoma [ 15 , 16 ]. In fact, these have mutations in common with endometriosis, such as PTEN , PIK3CA , KRAS and ARID1A [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, many studies confirm that the histotypes of epithelial ovarian cancer that are most closely related to endometriosis are endometrioid tumors and clear cell carcinoma [ 15 , 16 ]. In fact, these have mutations in common with endometriosis, such as PTEN , PIK3CA , KRAS and ARID1A [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Endometriosis-Related Ovarian Cancers: Evidence for a Dichotomy in the Histogenesis of the Two Associated Histotypes

et al. 2023

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Evidence indicates that different pathways of malignant degeneration underlie the development of endometriosis-associated ovarian tumors of endometrioid and clear cell histotypes. The aim of this study was to compare data from patients affected by these two histotypes to investigate the hypothesis of a dichotomy in the histogenesis of these tumors. Clinical data and tumor characteristics of 48 patients who were diagnosed with either pure clear cell ovarian cancer and mixed endometrioid–clear cell ovarian cancer arising from endometriosis (ECC, n = 22) or endometriosis-associated endometrioid ovarian cancer (EAEOC, n = 26) were compared. A previous diagnosis of endometriosis was detected more frequently in the ECC group (32% vs. 4%, p = 0.01). The incidence of bilaterality was significantly higher in the EAOEC group (35% vs. 5%, p = 0.01) as well as a solid/cystic rate at gross pathology (57.7 ± 7.9% vs. 30.9 ± 7.5%, p = 0.02). Patients with ECC had a more advanced disease stage (41% vs. 15%; p = 0.04). A synchronous endometrial carcinoma was detected in 38% of EAEOC patients. A comparison of the International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis showed a significantly decreasing trend for ECC compared to EAEOC (p = 0.02). These findings support the hypothesis that the origin, clinical behavior and relationship with endometriosis might be different for these histotypes. ECC, unlike EAEOC, seems to develop within an endometriotic cyst, thus representing a window of possibility for ultrasound-based early diagnosis.

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“…Neoadjuvant chemotherapy is considered for patients with extensive disease and having difficulty for complete cytoreduction. Despite standard treatment recurrence is very common in EOC and these recurrent tumors are not responsive to chemotherapy due to the development of the chemoresistance 2 . Among five different subtypes of EOC, High Grade Serous Ovarian Cancers (HG-SOC) is the dominant subtype diagnosed clinically, constitute majority (70%) of ovarian tumors and has poor 5 years survival rates of 5-30% despite the standard treatment.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BRCA1 expression, its correlation with clinicopathological features and response to neoadjuvant chemotherapy in high grade serous ovarian cancer from an Indian centre

Patil

et al. 2023

Preprint

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In high grade serous ovarian cancers (HG-SOC), BRCA1/2 mutations have been reported as the most predominant mutations by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We aimed to evaluate BRCA1 inactivation by estimating its expression along with its repressor in primary and neoadjuvant chemotherapy (NACT) treated HG-SOC tumors with known therapeutic response. The expression pattern of BRCA1 protein was evaluated by immunohistochemistry (IHC) in 119 cases of HG-SOC from a hospital cohort consisting of primary (N= 69) and NACT treated (N=50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs) and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4 was estimated by qPCR. Association of BRCA1 protein and mRNA with clinicopathological features was studied. Relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. BRCA1 protein expression was observed in 12% of primary and 19% of NACT treated HG-SOC tumors. Moderate concordance was observed between BRCA1 protein and mRNA expression (AUC-0.677). High BRCA1 mRNA expression was significantly associated with more frequent SET pattern (p=0.024), higher sTILs density (p=0.042), increased mitosis (p=0.028). BRCA1 negative tumors showed higher expression of ID4 though not statistically significant. Higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p=0.042) and NACT treated tumors (p=0.040). Our findings show the utility of BRCA1/ID4 ratio to predict neoadjuvant therapy response, which needs further evaluation in larger cohort with long term outcomes.

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Epithelial ovarian cancer: Review article

Cited by 54 publications

References 70 publications

The Drug Efficacy Testing in Ex Vivo 3D Cultures (DETECt) platform enables rapid identification of effective drugs and drug combinations for ovarian cancer patients

The Drug Efficacy Testing in Ex Vivo 3D Cultures (DETECt) platform enables rapid identification of effective drugs and drug combinations for ovarian cancer patients

Endometriosis-Related Ovarian Cancers: Evidence for a Dichotomy in the Histogenesis of the Two Associated Histotypes

BRCA1 expression, its correlation with clinicopathological features and response to neoadjuvant chemotherapy in high grade serous ovarian cancer from an Indian centre

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