scholarly journals c-MYC and Epithelial Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jeyshka M. Reyes-González ◽  
Pablo E. Vivas-Mejía
Keyword(s):  
Patient Outcome ◽  
Ovarian Cancer ◽  
Standard Of Care ◽  
Initial Response ◽  
Platinum Resistance ◽  
Therapy Regimen ◽  
Clinical Challenge ◽  
Tumor Types ◽  
Improve Patient

Ovarian cancer is the deadliest of gynecological malignancies with approximately 49% of women surviving 5 years after initial diagnosis. The standard of care for ovarian cancer consists of cytoreductive surgery followed by platinum-based combination chemotherapy. Unfortunately, despite initial response, platinum resistance remains a major clinical challenge. Therefore, the identification of effective biomarkers and therapeutic targets is crucial to guide therapy regimen, maximize clinical benefit, and improve patient outcome. Given the pivotal role of c-MYC deregulation in most tumor types, including ovarian cancer, assessment of c-MYC biological and clinical relevance is essential. Here, we briefly describe the frequency of c-MYC deregulation in ovarian cancer and the consequences of its targeting.

New biomarkers to predict platinum resistance in ovarian cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17085-e17085
Author(s):  
Oana Trifanescu ◽  
Laurentia Minea Gales ◽  
Maria Iuliana Gruia ◽  
Bianca Andreea Gusoiu ◽  
Florina Torliceanu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Roc Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Initial Response ◽  
Platinum Resistance ◽  
Platinum Sensitive ◽  
Platinum Salts ◽  
Platinum Based Chemotherapy

e17085 Background: Epithelial ovarian cancer is the second most common gynecologic malignancy and is characterized by the highest mortality of all gynecological cancers. Despite of initial response, platinum resistance develops and contributes to the poor outcome of advanced stage ovarian cancer patients. The aim of the study was to identify biomarkers helpful in predicting treatment response to platinum salts. Methods: Forty eight patients with advanced ovarian (stage II, III and IV) cancer were prospectively enrolled between 2014 and 2017. All patients underwent surgery followed by platinum-based chemotherapy. Serum reactive oxygen species parameters such as malondialdehyde, ceruloplasmine, and serum VEGF were measured before each cycle of chemotherapy. Results: Mean age at diagnostic was 51.3 +/- 8.1 years, (range 42 - 78). Median follow up was 39 months (range 12-56). Twenty tree percent were platinum resistance. Median progression free survival was 22 months and estimated median overall survival was 84 months, 77% of patients being alive at 3 years. VEGF levels were significantly higher in patients with platinum resistance disease (1210 pg/ml) compare to platinum sensitive (mean VEGF levels 945pg/ml, p = 0.0003). We used a ROC curve to estimate the sensitivity and specificity of VEGF as a predictor to platinum response and find out that the aria under the curve (AUC) was 0.874, p = 0.003, 95% CI 0.734-1 and cut-off value (80% sensibility, 80% specificity) was 1085pg/ml. Malondialdehyde levels were statistically significant higher in patients with platinum resistance disease (mean value 11.1 μmol/100 ml vs. 7.4 μmol/100 ml in platinum sensitive, p = 0.02. The ROC curve for malondialdehyde identify an aria under the curve of 0.818, p = 0.0001 and CI 95% (0.744-0.893) and a cut-off value of 7.74 μmol/100 ml to estimate with 81.3% sensitivity and 64% specificity platinum response validating this bio markers as predicting platinum response. For Ceruloplasmine AUC was 0.706, p = 0.0001, 95% CI (0.617,-0.796). Conclusions: Malondialdehyde, ceruloplasmine and VEGF can estimate with precision the resistance to platinum salts in advanced ovarian cancer patients.

scholarly journals The role of pemetrexed in recurrent epithelial ovarian cancer: A scoping review

2018 ◽  
Author(s):  
Michael Roche ◽  
Laura Parisi ◽  
Linda Li ◽  
Amy Knehans ◽  
Rebecca Phaeton ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Malignant Pleural Mesothelioma ◽  
Scoping Review ◽  
Initial Response ◽  
Pleural Mesothelioma ◽  
Advanced Stage ◽  
Gynecologic Malignancies ◽  
New Generation

Ovarian cancer is the leading cause of mortality among gynecologic malignancies, with most cases diagnosed at an advanced stage. Despite an initial response, most develop a recurrence and subsequent resistance to standard therapies. Pemetrexed (AlimtaTM) is a new generation multi-targeted antifolate initially approved for the treatment of malignant pleural mesothelioma. In recent years, it has shown promise in the treatment of recurrent epithelial ovarian cancer. In this review, we outline the current literature and discuss the future of pemetrexed in the setting of recurrent epithelial ovarian cancer.

scholarly journals Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3035
Author(s):  
Alessandra Dall'Acqua ◽  
Michele Bartoletti ◽  
Nastaran Masoudi-Khoram ◽  
Roberto Sorio ◽  
Fabio Puglisi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Therapeutic Targets ◽  
Metastatic Breast ◽  
Molecular Alterations ◽  
Estrogen Receptor Positive ◽  
Cancer Types ◽  
Almost All ◽  
Tumor Types

Alterations in components of the cell-cycle machinery are present in essentially all tumor types. In particular, molecular alterations resulting in dysregulation of the G1 to S phase transition have been observed in almost all human tumors, including ovarian cancer. These alterations have been identified as potential therapeutic targets in several cancer types, thereby stimulating the development of small molecule inhibitors of the cyclin dependent kinases. Among these, CDK4 and CDK6 inhibitors confirmed in clinical trials that CDKs might indeed represent valid therapeutic targets in, at least some, types of cancer. CDK4 and CDK6 inhibitors are now used in clinic for the treatment of patients with estrogen receptor positive metastatic breast cancer and their clinical use is being tested in many other cancer types, alone or in combination with other agents. Here, we review the role of CDK4 and CDK6 complexes in ovarian cancer and propose the possible use of their inhibitors in the treatment of ovarian cancer patients with different types and stages of disease.

scholarly journals Special Agents Hunting Down Women Silent Killer: The Emerging Role of the p38αKinase

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Valentina Grossi ◽  
Cristiano Simone
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Metabolic Reprogramming ◽  
Proliferating Cells ◽  
Improve Patient Survival ◽  
High Incidence ◽  
Current Therapies ◽  
Therapy Success ◽  
Improve Patient

Ovarian cancer is sensitive to chemotherapy with platinum compounds; however, the therapy success rate is significantly lowered by a high incidence of recurrence and by the acquisition of drug resistance. These negative outcomes mainly depend on altered apoptotic and drug resistance pathways, determining the need for the design of new therapeutic strategies to improve patient survival. This challenge has become even more critical because it has been recognized that hindering uncontrolled cell growth is not sufficient as the only curative approach. In fact, while current therapies are mostly conceived to impair survival of highly proliferating cells, several lines of research are now focusing on cancer-specific features to specifically target malignant cells with the aim of avoiding drug resistance and reducing adverse effects. Recently, great interest has been generated by the identification of metabolic reprogramming mechanisms occurring in cancer cells, such as the increase in glycolysis levels. In this light, pharmacologic manipulation of relevant pathways involved in cancer-specific metabolism and drug resistance could prove an effective approach to treat ovarian cancer patients.

scholarly journals Optimized detection of somatic allelic imbalances specific for homologous recombination deficiency improves the prediction of clinical outcomes in ovarian cancer

2021 ◽  
Author(s):  
Fernando Ramon Perez-Villatoro ◽  
Julia Casado ◽  
Anniina Farkkila
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Clinical Outcomes ◽  
Repair Deficiency ◽  
Improve Patient Selection ◽  
Dna Repair Deficiency ◽  
Tumor Types ◽  
Improve Patient ◽  
Pan Cancer

Specific patterns of genomic allelic imbalances (AIs) have been associated with Homologous recombination DNA-repair deficiency (HRD). We performed a systematic pan-cancer characterization of AIs across tumor types, revealing unique patterns in ovarian cancer. Using machine learning on a multi-omics dataset, we generated an optimized algorithm to detect HRD in ovarian cancer (ovaHRDscar). ovaHRDscar improved the prediction of clinical outcomes in three independent validation cohorts (PCAWG, HERCULES, TERVA). Characterization of 98 spatiotemporally distinct tumor samples indicated ovary/adnex as the preferred site to assess HRD. In conclusion, ovaHRDscar improves the detection of HRD in ovarian cancer with the premise to improve patient selection for HR-targeted therapies.

scholarly journals The role of patient-derived ovarian cancer organoids in the study of PARP inhibitors sensitivity and resistance: from genomic analysis to functional testing

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mengyu Tao ◽  
Xia Wu
Keyword(s):  
Ovarian Cancer ◽  
Genomic Analysis ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Parp Inhibitors ◽  
Functional Testing ◽  
Functional Assays ◽  
Genetic Features ◽  
Next Generation Sequencing Ngs

AbstractEpithelial ovarian cancer (EOC) harbors distinct genetic features such as homologous recombination repair (HRR) deficiency, and therefore may respond to poly ADP-ribose polymerase inhibitors (PARPi). Over the past few years, PARPi have been added to the standard of care for EOC patients in both front-line and recurrent settings. Next-generation sequencing (NGS) genomic analysis provides key information, allowing for the prediction of PARPi response in patients who are PARPi naïve. However, there are indeed some limitations in NGS analyses. A subset of patients can benefit from PARPi, despite the failed detection of the predictive biomarkers such as BRCA1/2 mutations or HRR deficiency. Moreover, in the recurrent setting, the sequencing of initial tumor does not allow for the detection of reversions or secondary mutations restoring proficient HRR and thus leading to PARPi resistance. Therefore, it becomes crucial to better screen patients who will likely benefit from PARPi treatment, especially those with prior receipt of maintenance PARPi therapy. Recently, patient-derived organoids (PDOs) have been regarded as a reliable preclinical platform with clonal heterogeneity and genetic features of original tumors. PDOs are found feasible for functional testing and interrogation of biomarkers for predicting response to PARPi in EOC. Hence, we review the strengths and limitations of various predictive biomarkers and highlight the role of patient-derived ovarian cancer organoids as functional assays in the study of PARPi response. It was found that a combination of NGS and functional assays using PDOs could enhance the efficient screening of EOC patients suitable for PARPi, thus prolonging their survival time.

scholarly journals Critical role of Wnt/β-catenin signaling in driving epithelial ovarian cancer platinum resistance

Oncotarget ◽  
2015 ◽  
Vol 6 (27) ◽  
pp. 23720-23734 ◽  
Author(s):  
Anil Belur Nagaraj ◽  
Peronne Joseph ◽  
Olga Kovalenko ◽  
Sareena Singh ◽  
Amy Armstrong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Critical Role ◽  
Platinum Resistance

scholarly journals Genomic-Based Therapy of Gynecologic Malignancies

2019 ◽  
Vol 48 (1) ◽  
pp. 84
Author(s):  
Maurie Markman
Keyword(s):  
Ovarian Cancer ◽  
Care Delivery ◽  
Advanced Ovarian Cancer ◽  
Standard Of Care ◽  
Parp Inhibitors ◽  
Current Status ◽  
Gynecologic Malignancies ◽  
Substantial Progress ◽  
Recurrent Endometrial Cancer ◽  
Tumor Types

<p>This paper will review the current status of genomic-based therapy of gynecologic malignancies. The routine “standard-of-care” delivery of targeted therapeutics based on the presence of specific molecular biomarkers in the management of the gynecologic malignancies has been delayed compared to the substantial progress made in several other tumor types.  However, relatively recently reported and rather robust phase 3 trial data have confirmed a potentially major role for PARP inhibitors as both active treatment and maintenance therapy of advanced ovarian cancer.  Further, data demonstrating the presence of a specific molecular phenotype (micro-satellite instability high – MSI-H) is a valid biomarker for the potential clinical utility of checkpoint inhibitor immunotherapy has relevance for all gynecologic malignancies, and particularly in the setting of metastatic or recurrent endometrial cancer.</p><p><strong>Conclusions. </strong>The introduction of PARP inhibitors into the oncology armamentarium has substantially impacted standard-of-care strategies in the management of ovarian cancer. It is anticipated that the results of ongoing and future trials will further define the role of genomic-based therapy in ovarian cancer and other gynecologic malignancies.</p>

scholarly journals Biomarkers of platinum resistance in ovarian cancer: what can we use to improve treatment

2018 ◽  
Vol 25 (5) ◽  
pp. R303-R318 ◽  
Author(s):  
Belinda van Zyl ◽  
Denise Tang ◽  
Nikola A Bowden
Keyword(s):  
Ovarian Cancer ◽  
Survival Rates ◽  
Chemotherapy Resistance ◽  
Initial Response ◽  
Disease Recurrence ◽  
Future Research ◽  
Platinum Resistance ◽  
Platinum Resistant ◽  
New Treatments ◽  
Platinum Chemotherapy

Ovarian cancer has poor survival rates due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High-grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60–80%, but eventually the majority of patients become platinum-resistant with subsequent relapses. Extensive research on individual biomarkers of platinum resistance has revealed many potential targets for the development new treatments. While this is ongoing, there are also epigenetic, DNA repair, genome and immune changes characterised in platinum-resistant HGSOC that can be targeted with current therapies. This review discusses biomarkers of platinum chemotherapy resistance in ovarian cancer with a focus on biomarkers that are targetable with alternative treatment combinations to those currently used. After decades of research focused on elucidating the biological cause of platinum resistance, future research needs to focus on using this knowledge to overcome resistance for patients with ovarian cancer.

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