Surgical prevention strategies in ovarian cancer

Mallen, Adrianne; Soong, Thing Rinda; Townsend, Mary K.; Crum, Christopher P.; Tworoger, Shelley S.

doi:10.1016/j.ygyno.2018.08.005

Cited by 43 publications

(32 citation statements)

References 107 publications

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“…It comprises five main described subtypes: HGSOC, low-grade serous ovarian carcinoma (LGSOC), endometrioid, clear cell and mucinous. In recent years, evidence has shown that each type has unique molecular features, treatment response and prognosis [25]. In contrast, the current classification combines molecular genetics and clinical features and describes two major types of ovarian cancer: type I includes LGSOC, endometrioid, clear cell and mucinous OCs, while type II comprises HGSOC, the principal component, and nonepithelial OC [26,27].…”

Section: Origin and Molecular Features Of Ocmentioning

confidence: 99%

Targeting Cancer Stem Cells to Overcome Therapy Resistance in Ovarian Cancer

Muñoz-Galván

Carnero

2020

Cells

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Ovarian cancer is the most lethal gynecological malignancy due to its late detection and high recurrence rate. Resistance to conventional platinum-based therapies and metastasis are attributed to a population of cells within tumors called cancer stem cells, which possess stem-like features and are able to recapitulate new tumors. Recent studies have deepened the understanding of the biology of ovarian cancer stem cells and their special properties and have identified multiple markers and signaling pathways responsible for their self-renewal abilities. Targeting cancer stem cells represents the most promising strategy for overcoming therapy resistance and reducing mortality in ovarian cancer, but further efforts must be made to improve our understanding of the mechanisms involved in therapy resistance. In this review, we summarize our current knowledge about ovarian cancer stem cells, their involvement in metastasis and their interactions with the tumor microenvironment; we also discuss the therapeutic approaches that are being developed to target them to prevent tumor relapse.

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Section: Origin and Molecular Features Of Ocmentioning

confidence: 99%

Targeting Cancer Stem Cells to Overcome Therapy Resistance in Ovarian Cancer

Muñoz-Galván

Carnero

2020

Cells

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“…Hormonal and reproductive factors are considered among the most significant risk factors for the development of OC. Early menarche or late menopause onset have been associated with a higher OC risk, suggesting that the ovulation-related proinflammatory response may promote malignant transformation and development of this gynecologic disease [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. As a consequence, pregnancy, breastfeeding, and early menopause that preclude the ovulation, represent protective factors and can decrease the risk of OC developing [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

An Overview of Candidate Therapeutic Target Genes in Ovarian Cancer

Alexandrova

Pecoraro

Sellitto

et al. 2020

Cancers

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Ovarian cancer (OC) shows the highest mortality rate among gynecological malignancies and, because of the absence of specific symptoms, it is frequently diagnosed at an advanced stage, mainly due to the lack of specific and early biomarkers, such as those based on cancer molecular signature identification. Indeed, although significant progress has been made toward improving the clinical outcome of other cancers, rates of mortality for OC are essentially unchanged since 1980, suggesting the need of new approaches to identify and characterize the molecular mechanisms underlying pathogenesis and progression of these malignancies. In addition, due to the low response rate and the high frequency of resistance to current treatments, emerging therapeutic strategies against OC focus on targeting single factors and pathways specifically involved in tumor growth and metastasis. To date, loss-of-function screenings are extensively applied to identify key drug targets in cancer, seeking for more effective, disease-tailored treatments to overcome lack of response or resistance to current therapies. We review here the information relative to essential genes and functional pathways recently discovered in OC, often strictly interconnected with each other and representing promising biomarkers and molecular targets to treat these malignancies.

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“…The clinical response rates to these drugs regularly exceed 60%, and the median time to the onset of recurrence usually exceeds 1 year even in the subset of women with suboptimal cytoreduction [2, 7–9]. In spite of surgery and chemotherapy administration, approximately 80% of the patients will relapse.…”

Section: Introductionmentioning

confidence: 99%

New markers for human ovarian cancer that link platinum resistance to the cancer stem cell phenotype and define new therapeutic combinations and diagnostic tools

Muñoz-Galván

Felipe‐Abrio

García-Carrasco

et al. 2019

J Exp Clin Cancer Res

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Background Ovarian cancer is the leading cause of gynecologic cancer-related death, due in part to a late diagnosis and a high rate of recurrence. Primary and acquired platinum resistance is related to a low response probability to subsequent lines of treatment and to a poor survival. Therefore, a comprehensive understanding of the mechanisms that drive platinum resistance is urgently needed. Methods We used bioinformatics analysis of public databases and RT-qPCR to quantitate the relative gene expression profiles of ovarian tumors. Many of the dysregulated genes were cancer stem cell (CSC) factors, and we analyzed its relation to therapeutic resistance in human primary tumors. We also performed clustering and in vitro analyses of therapy cytotoxicity in tumorspheres. Results Using bioinformatics analysis, we identified transcriptional targets that are common endpoints of genetic alterations linked to platinum resistance in ovarian tumors. Most of these genes are grouped into 4 main clusters related to the CSC phenotype, including the DNA damage, Notch and C-KIT/MAPK/MEK pathways. The relative expression of these genes, either alone or in combination, is related to prognosis and provide a connection between platinum resistance and the CSC phenotype. However, the expression of the CSC-related markers was heterogeneous in the resistant tumors, most likely because there were different CSC pools. Furthermore, our in vitro results showed that the inhibition of the CSC-related targets lying at the intersection of the DNA damage, Notch and C-KIT/MAPK/MEK pathways sensitize CSC-enriched tumorspheres to platinum therapies, suggesting a new option for the treatment of patients with platinum-resistant ovarian cancer. Conclusions The current study presents a new approach to target the physiology of resistant ovarian tumor cells through the identification of core biomarkers. We hypothesize that the identified mutations confer platinum resistance by converging to activate a few pathways and to induce the expression of a few common, measurable and targetable essential genes. These pathways include the DNA damage, Notch and C-KIT/MAPK/MEK pathways. Finally, the combined inhibition of one of these pathways with platinum treatment increases the sensitivity of CSC-enriched tumorspheres to low doses of platinum, suggesting a new treatment for ovarian cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1245-5) contains supplementary material, which is available to authorized users.

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Surgical prevention strategies in ovarian cancer

Cited by 43 publications

References 107 publications

Targeting Cancer Stem Cells to Overcome Therapy Resistance in Ovarian Cancer

Targeting Cancer Stem Cells to Overcome Therapy Resistance in Ovarian Cancer

An Overview of Candidate Therapeutic Target Genes in Ovarian Cancer

New markers for human ovarian cancer that link platinum resistance to the cancer stem cell phenotype and define new therapeutic combinations and diagnostic tools

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