Epigenetic Modifications in Ovarian Cancer: A Review

Ashraf, Aqsa; Afroze, Syeda H.; Osuji, Grace; Kayani, Saba; Colon, Natalie; Pantho, Ahmed; Kuehl, Thomas J.; Pilkinton, Kimberly; Uddin, Mohammad M.

doi:10.29245/2578-2967/2020/2.1179

Cited by 10 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Identification of somatic mutations in cancer is generally associated with a better prognosis then cancers involving pathogenic or likely pathogenic germline variants. Additionally, epigenetic causes of HRD involve the silencing of BRCA genes by up or down regulated miRNA activity or BRCA promoter hypermethylation [45]. Analogous miR-1255b, miR-148b, and miR-193b miRNA molecules targeting BRCAness genes have been described in ovarian cancer [46].…”

Section: Homologous Recombination Dna Repair Proficiency (Hrp) and Cancermentioning

confidence: 99%

Homologous recombination proficiency in ovarian and breast cancer patients

et al. 2021

View full text Add to dashboard Cite

Homologous recombination and DNA repair are important for genome maintenance. Genetic variations in essential homologous recombination genes, including BRCA1 and BRCA2 results in homologous recombination deficiency (HRD) and can be a target for therapeutic strategies including poly (ADP-ribose) polymerase inhibitors (PARPi). However, response is limited in patients who are not HRD, highlighting the need for reliable and robust HRD testing. This manuscript will review BRCA1/2 function and homologous recombination proficiency in respect to breast and ovarian cancer. The current standard testing methods for HRD will be discussed as well as trials leading to approval of PARPi’s. Finally, standard of care treatment and synthetic lethality will be reviewed.

show abstract

Section: Homologous Recombination Dna Repair Proficiency (Hrp) and Cancermentioning

confidence: 99%

Homologous recombination proficiency in ovarian and breast cancer patients

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Furthermore, there is evidence that patients with tumors with high clonal expansion of these stem cells have shorter disease-free intervals and shorter survival [35]. Mutational profiling of recurrent disease has identified extensive intertumoral heterogeneity and genomic instability, which allows for the formation of these chemoresistant clones [25,37,38].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, the demethylation of tumor suppressor genes such as p53, MLH1, p16 and others also contributes to the genetic instability responsible for the development of HGSC [24]. These epigenetic changes provide the framework for the development of cancer chemoresistance, proliferation and metastasis [25]. Furthermore, there is evidence that epigenetic drugs, which modify these epigenetic changes, are not only directly cytotoxic, but can make classic chemotherapy more effective by reversing chemoresistance [26].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time

et al. 2021

View full text Add to dashboard Cite

Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients’ lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture.

show abstract

“…Another important component includes epigenetic modifications which result in silencing as well as activation of gene expression without DNA sequence alteration [36]. The majority of cancers, including ovarian cancer, have aberrant epigenetic modifications which result in the promotion of cancer growth, metastasis and chemoresistance [37].…”

Section: Can Epigenetic Therapy Overcome Ovarian Cancer Chemoresistance?mentioning

confidence: 99%

Novel Indications of Epigenetic Therapy in Ovarian Cancer

Griffiths¹,

Bilbao²,

Krill³

et al. 2021

Ovarian Cancer - Updates in Tumour Biology and Therapeutics [Working Title]

View full text Add to dashboard Cite

Early diagnosis and intervention are some of the longstanding challenges associated with ovarian cancer, which is the leading cause of gynecologic cancer mortality. While the majority of patients who present with advanced stage disease at time of diagnosis will initially respond to traditional combination platinum and taxane-based chemotherapy in conjunction with cytoreductive surgery, approximately 70% will ultimately recur due to chemoresistance within the first two years. Intratumor heterogeneity is proposed to be a leading factor in the development of chemoresistance and resultant poorer outcomes for those with recurrent or advanced stage disease. Both inherent and acquired mechanisms of chemoresistance are postulated to be a result of alterations in gene expression, also known as epigenetic modifications. Therefore, epigenetic therapy is a pivotal avenue which allows for reversal of chemoresistance in cancer through the targeting of aberrant mutations. In this chapter, we discuss how these epigenetic modifications prove to be promising targets in cancer therapy leading to heightened drug sensitivity and improved patient survival outcomes.

show abstract

Epigenetic Modifications in Ovarian Cancer: A Review

Cited by 10 publications

References 0 publications

Homologous recombination proficiency in ovarian and breast cancer patients

Homologous recombination proficiency in ovarian and breast cancer patients

Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time

Novel Indications of Epigenetic Therapy in Ovarian Cancer

Contact Info

Product

Resources

About