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https://www.readbyqxmd.com/read/29784743/new-therapies-for-ovarian-cancer
#1
Deborah K Armstrong
In the latest NCCN Guidelines for Ovarian Cancer, the histologic subtypes of ovarian cancer are described in more depth as they vary by frequency, typical age and disease stage at presentation, treatment recommendations, and survival probabilities. The less common subtypes are also discussed. The update with the greatest impact on the treatment of ovarian cancer, however, is probably the use of maintenance therapy with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and 3 PARP inhibitors are now included in the guidelines...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29774075/plectin-targeted-liposomes-enhance-the-therapeutic-efficacy-of-a-parp-inhibitor-in-the-treatment-of-ovarian-cancer
#2
Siva Sai Krishna Dasa, Galina Diakova, Ryo Suzuki, Anne M Mills, Michael F Gutknecht, Alexander L Klibanov, Jill K Slack-Davis, Kimberly A Kelly
Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise...
2018: Theranostics
https://www.readbyqxmd.com/read/29767688/safety-and-dose-modification-for-patients-receiving-niraparib
#3
J S Berek, U A Matulonis, U Peen, P Ghatage, S Mahner, A Redondo, A Lesoin, N Colombo, I Vergote, O Rosengarten, J Ledermann, M Pineda, S Ellard, J Sehouli, A Gonzalez-Martin, D Berton-Rigaud, R Madry, A Reinthaller, S Hazard, W Guo, M R Mirza
Background: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved in the United States and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to TEAE was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was performed to identify clinical parameters that predict dose reductions...
May 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29767248/combined-treatment-with-pi3k-inhibitor-bkm120-and-parp-inhibitor-olaparib-is-effective-in-inhibiting-the-gastric-cancer-cells-with-arid1a-deficiency
#4
Lin Yang, Guanghai Yang, Yingjun Ding, Yu Huang, Shunfang Liu, Lei Zhou, Wenjie Wei, Jing Wang, Guangyuan Hu
Dual blockade of phosphoinositide 3-kinase (PI3K) and poly(ADP-ribose) polymerase (PARP) has been revealed to be an effective treatment strategy for breast, ovarian and prostate cancer. However, the efficacy of this combination for the treatment of gastric cancer, and potential predictive therapeutic biomarkers remain unclear. Recent evidence suggests that the deficiency of AT-rich interactive domain containing protein 1A (ARID1A), which is a crucial chromatin remodeling gene, sensitizes tumor cells to PI3K and PARP inhibitors...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29758486/poly-i-c-and-lps-induce-distinct-immune-responses-by-ovarian-stromal-fibroblasts
#5
Mickey V Patel, Zheng Shen, Charles R Wira
Despite its anatomical location, the ovary is a site of pathogen exposure in the human female reproductive tract (FRT). However, the role of ovarian stromal fibroblasts in immune protection is unclear. We generated a population of ovarian stromal fibroblasts derived from normal human ovaries that expressed the pattern recognition receptors TLR3, TLR4, RIG-I, & MDA5. Poly (I:C) and LPS, respective mimics of viral and bacterial infections, selectively upregulated antiviral gene expression and secretion of chemokines and antimicrobials...
May 9, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29750868/brca-status-does-not-predict-synergism-of-a-carboplatin-and-olaparib-combination-in-high-grade-serous-ovarian-cancer-cell-lines
#6
Yen Ting Shen, James C Evans, Gaetano Zafarana, Christine Allen, Micheline Piquette-Miller
Over 50% of epithelial ovarian cancers express the BRCAness profile that leads to a dysfunctional homologous recombination repair system. The combination of a dysfunctional homologous recombination repair system and a poly (ADP-ribose) polymerase (PARP) inhibitor results in a synthetic lethal phenotype. The PARP inhibitor olaparib, approved as a monotherapy for patients with a germline BRCA mutation, has shown promising results in preclinical studies when combined with DNA damaging agents such as carboplatin...
May 11, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29750420/latest-clinical-evidence-and-further-development-of-parp-inhibitors-in-ovarian-cancer
#7
M R Mirza, S Pignata, J A Ledermann
Background: For several decades, the systemic treatment of ovarian cancer has involved chemotherapy, with the relatively recent addition of anti-angiogenic strategies given with chemotherapy and in the maintenance setting. In the past decade, numerous poly(ADP-ribose) polymerase (PARP)-inhibiting agents have been assessed. Design: We review key trials that have led to the approval of three PARP inhibitors - olaparib, niraparib and rucaparib - as maintenance therapy for platinum-sensitive recurrent ovarian cancer...
May 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29735311/inadequate-rates-of-brca-testing-with-its-negative-consequences-for-women-with-epithelial-ovarian-cancer-and-their-families-an-overview-of-the-literature
#8
P J Hoskins
Fifteen per cent of women with epithelial ovarian cancer possess inherited mutations in the BRCA genes. Knowledge of her BRCA status is important to her and her family. Poly(ADP-ribose) polymerase (PARP) inhibitors provide a new therapeutic option for her. For her family it provides the opportunity for the prevention of what otherwise is often a lethal disease. To access these opportunities, the mandatory first step is testing the woman with the cancer. However, referral rates for genetic counselling and subsequent BRCA testing are low, in the of 10-30% range...
May 5, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29733524/safety-and-pharmacokinetics-of-veliparib-extended-release-in-patients-with-advanced-solid-tumors-a-phase-i-study
#9
Theresa L Werner, Jasgit Sachdev, Elizabeth M Swisher, Martin Gutierrez, Muaiad Kittaneh, Mark N Stein, Hao Xiong, Martin Dunbar, Danielle Sullivan, Philip Komarnitsky, Mark McKee, Antoinette R Tan
The poly(ADP-ribose) polymerase-1/2 inhibitor veliparib is active against tumors deficient in homologous DNA damage repair. The pharmacokinetics and safety of veliparib extended-release (ER) were evaluated in patients with advanced solid tumors. This phase I study assessed veliparib-ER up to 800 mg once daily or 600 mg twice daily. Dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), and maximum tolerated dose (MTD) were assessed in cycle 1 and safety/tolerability during continuous administration (28-day cycles)...
May 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29731958/main-implications-related-to-the-switch-to-brca-1-2-tumor-testing-in-ovarian-cancer-patients-a-proposal-of-a-consensus
#10
Ettore Capoluongo, Giovanni Scambia, Jean-Marc Nabholtz
Background: Since the approval of the first poly (adenosine diphosphate [ADP]) ribose polymerase inhibitor (PARPi; olaparib [Lynparza™]) for platinum-sensitive relapsed high grade ovarian cancer, with either germline or somatic BRCA1/2 deleterious variants, the strategies for BRCA1/2 are dynamically changing. Along with germline testing within the context of familial or sporadic ovarian cancer, patients are now being referred for BRCA1/2 genetic assay above all for treatment decisions: in this setting tumour BRCA assay can allow to identify an estimated 3-9% of patients with peculiar somatic BRCA1/2 mutations...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29729664/complete-response-to-orally-administered-melphalan-in-malignant-pleural-effusion-from-an-occult-female-genital-organ-primary-neoplasm-with-brca1-2-mutations-a-case-report
#11
Frank S Fan, Chung-Fan Yang
BACKGROUND: Definite diagnosis of metastasis from unknown primary depends on a comprehensive immunohistochemical investigation of tumor specimen. Accurate identification of the origin site usually helps a lot in choosing the most appropriate treatment. Molecular characterization provides more chance of a cure. Echoing modern medical development, BRCA1/2 mutations have been correlated with high efficiency of poly(adenosine diphosphate-ribose) polymerase inhibitors in ovarian cancer. While a previous case report demonstrated a surprising cure of platinum-resistant ovarian cancer with BRCA2 mutation by orally administered melphalan...
May 6, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29729631/formulation-and-optimization-of-topotecan-nanoparticles-in-vitro-characterization-cytotoxicity-cellular-uptake-and-pharmacokinetic-outcomes
#12
Santwana Padhi, Rohit Kapoor, Devina Verma, Amulya K Panda, Zeenat Iqbal
The study focuses on widening up the therapeutic perspective of anti-cancer therapy by entrapping a hydrophilic anticancer drug, topotecan hydrochloride (TOPO) in biodegradable poly (lactide-co-glycolide) (PLGA) matrix to form topotecan nanoparticles (TOPO NPs) by a double emulsion solvent evaporation technique. Statistical optimization using Box-Behnken design showed that sonication time of primary emulsion for 120 s, drug: polymer ratio of 1:12.65, organic phase: external aqueous phase ratio of 1:2.82 and 0...
April 16, 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29725407/the-enhanced-delivery-of-salinomycin-to-cd133-ovarian-cancer-stem-cells-through-cd133-antibody-conjugation-with-poly-lactic-co-glycolic-acid-poly-ethylene-glycol-nanoparticles
#13
Yi Mi, Yuqin Huang, Jie Deng
Ovarian cancer is the most lethal gynecologic malignancy, and ovarian cancer stem cells (CSCs) serve a pivotal function in the metastasis and recurrence of ovarian cancer. Multiple previous studies have validated CD133 as a marker of ovarian CSCs. Although salinomycin is a promising therapeutic agent that has been demonstrated to kill CSCs in various types of cancer, poor aqueous solubility hampers its clinical application. The present study used salinomycin-loaded poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles conjugated with CD133 antibodies (CD133-SAL-NP) to eliminate CD133+ ovarian CSCs...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29664016/the-evolving-landscape-of-predictive-biomarkers-of-response-to-parp-inhibitors
#14
Anish Thomas, Junko Murai, Yves Pommier
Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis - olaparib, niraparib, and rucaparib - were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response...
May 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29660759/parp-inhibitors-in-breast-cancer-bringing-synthetic-lethality-to-the-bedside
#15
REVIEW
Anita A Turk, Kari B Wisinski
Individuals with breast and ovarian cancer susceptibility gene 1 (BRCA1) or BRCA2 germline mutations have a significantly increased lifetime risk for breast and ovarian cancers. BRCA-mutant cancer cells have abnormal homologous recombination (HR) repair of DNA. In these tumors, the base excision repair (BER) pathway is important for cell survival. The poly(adenosine diphosphate-ribose) polymerase (PARP) enzymes play a key role in BER, and PARP inhibitors are effective in causing cell death in BRCA-mutant cells while sparing normal cells-a concept called synthetic lethality...
April 16, 2018: Cancer
https://www.readbyqxmd.com/read/29650751/fda-approval-summary-niraparib-for-the-maintenance-treatment-of-patients-with-recurrent-ovarian-cancer-in-response-to-platinum-based-chemotherapy
#16
Gwynn Ison, Lynn J Howie, Laleh Amiri-Kordestani, Lijun Zhang, Shenghui Tang, Rajeshwari Sridhara, Vadryn Pierre, Rosane Charlab, Anuradha Ramamoorthy, Pengfei Song, Fang Li, Jingyu Yu, Wimolnut Manheng, Todd R Palmby, Soma Ghosh, Hisani N Horne, Eunice Y Lee, Reena Philip, Kaushalkumar Dave, Xiao Hong Chen, Sharon L Kelly, Kumar G Janoria, Anamitro Banerjee, Okponanabofa Eradiri, Jeannette Dinin, Kirsten B Goldberg, William F Pierce, Amna Ibrahim, Paul G Kluetz, Gideon M Blumenthal, Julia A Beaver, Richard Pazdur
The Food and Drug Administration approved niraparib, a poly ADP ribose polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in each cohort was the primary endpoint...
April 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29627080/assessment-and-management-of-diarrhea-following-vegf-receptor-tki-treatment-in-patients-with-ovarian-cancer
#17
REVIEW
Joyce Liu, Shibani Nicum, Peter Reichardt, Kenneth Croitoru, Beate Illek, Manuela Schmidinger, Catherine Rogers, Christin Whalen, Gordon C Jayson
Angiogenesis is a proven clinical target for the treatment of advanced epithelial ovarian cancer. Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) offer patients potential new treatment regimens as they can be given as monotherapy, in combination with poly(ADP-ribose) polymerase (PARP) inhibitors, or with and following cytotoxic chemotherapy. If VEGFR-TKIs are licensed for use in ovarian cancer, patients will require prompt and effective management of adverse events, including diarrhea, to optimize compliance and benefit...
April 4, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29625193/icaritin-induces-ovarian-cancer-cell-apoptosis-through-activation-of-p53-and-inhibition-of-akt-mtor-pathway
#18
Lvfen Gao, Ming Chen, Yuan Ouyang, Ruobin Li, Xian Zhang, Xuesong Gao, Xiaoyu Wang, Shaoqiang Lin
AIMS: Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers. Currently, the first-line OC treatment consists of cytoreductive surgery and platinum-based chemotherapy. However, most patients develop chemoresistance after the first-line treatment limits the success of treatment. Therefore, there is an urgent need to identify effective therapeutic agents. MAIN METHODS: Cell viabilities were detected by MTS assay; Annexin V-FITC/PI assay and western blotting assay were performed to analyze the apoptotic cells in vitro; An immunofluorescence assay was performed to analyze the TUNEL+ apoptotic cells in vivo; Patient-derived xenografts were established to test the in vivo antitumor effects; The key proteins of p53, caspase-mediated apoptotic pathway and Akt/mTOR pathway were detected by Western blotting...
April 3, 2018: Life Sciences
https://www.readbyqxmd.com/read/29620474/pharmacokinetic-drug-evaluation-of-niraparib-for-the-treatment-of-ovarian-cancer
#19
Teresa C Longoria, Krishnansu S Tewari
Ovarian cancer is a disease with a propensity to recur despite dramatic responses to initial treatment, which typically consists of a combination of cytoreductive surgery and platinum-based chemotherapy. A maintenance therapy, which may prevent or delay relapse while not negatively impacting quality of life, is critical to improving outcomes. Areas covered: This review discusses the pharmacologic properties, clinical efficacy, and safety profile of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy...
April 5, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29617063/folate-conjugated-polymeric-micelle-hb-loaded-on-targeting-effect-by-intraperitoneal-to-ovarian-cancer-in-vitro-and-in-vivo
#20
Jie Li, Shu Yao, Kai Wang, Zaijun Lu, Xuantao Su, Li Li, Cunzhong Yuan, Jinbo Feng, Shi Yan, Beihua Kong, Kun Song
Photodynamic therapy (PDT) is considered as an innovative and attractive modality to treat ovarian cancer. In this study, a biodegradable polymer poly (ethylene glycol)-poly (lactic acid)(PLA)-folate (FA-PEG-PLA) was prepared in order to synthesize an active targeting, water soluble and pharmacomodulated photosensitizer nano-carriers. The drug loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which HB/FA-PEG-PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (p<0...
April 4, 2018: Cancer Science
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