DOCSLIB.ORG

Current Ovarian Cancer Maintenance Strategies and Promising New

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Current Ovarian Cancer Maintenance Strategies and Promising New Journal of Cancer 2021, Vol. 12 38 Ivyspring International Publisher Journal of Cancer 2021; 12(1): 38-53. doi: 10.7150/jca.49406 Review Current Ovarian Cancer Maintenance Strategies and Promising New Developments Vinaya Gogineni1, Susan Morand1, Hannah Staats1, Rachel Royfman1, Monika Devanaboyina1, Katelyn Einloth1, Danielle Dever1, Laura Stanbery2, Phylicia Aaron2, Luisa Manning2, Adam Walter3, Gerald Edelman1, Lance Dworkin1, John Nemunaitis2 1. University of Toledo Medical Center, Toledo, OH 2. Gradalis, Inc, Carrollton, TX 3. Promedica Health System, Toledo, OH Corresponding author: John Nemunaitis, MD. [email protected] © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2020.06.12; Accepted: 2020.10.17; Published: 2021.01.01 Abstract While ovarian cancer typically responds well to front line treatment, many patients will relapse within 5 years. Treatment options are less effective at each recurrence highlighting the need for novel maintenance therapies. PolyADP-ribose polymerase (PARP) inhibitors have recently gained approval in ovarian cancer maintenance. Niraparib was approved regardless of BRCA mutation status, however impact on overall survival is limited. Oliparib was approved for BRCA mutant and BRCA wildtype/homologous recombination deficient patients. This review will focus on current frontline ovarian cancer treatment as well molecularly based approaches to ovarian cancer management. Key words: ovarian cancer maintenance, HGSOC, ovarian cancer treatment, Vigil Introduction Therapeutic management of ovarian cancer is consists of surgery in conjunction with chemotherapy. complex. A multitude of risk factors including, Ovarian cancer usually metastasizes first within the inherited mutations that vary in penetrance, somatic peritoneal cavity, and surgical debulking informs mutations, hormonal effect related to older onset of staging and adjuvant therapy. Multiple studies have menopause, relationship of exposure to environ- shown a relationship between the amount of residual mental hazards, and/or associated gynecological tumor following debulking surgery and response factors, such as pelvic inflammatory disease, rates [4]. The goal of surgical debulking is to leave the endometriosis and polycystic ovarian syndrome patient with no visible sites of disease therefore, complicate management and preventive care [1]. guidelines for optimal debulking have been adopted. Epithelial ovarian cancer is the most common Optimal debulking is defined as the largest residual subtype, comprising roughly 90% of the cases. tumor nodule measuring less than 1cm, while Moreover, due to site of presentation it often presents suboptimal debulking is when residual tumor is at late stage resulting in a poor 5 year survival rate greater than 1cm [5]. Debulking surgery can be even with optimal care [2, 3]. We will review sandwiched with neoadjuvant chemotherapy or preventive, therapeutic and future advances with a chemotherapy can be administered following primary focus on frontline maintenance therapy and the debulking surgery. Platinum containing doublet molecular relationship of ovarian cancer biology to therapy either intravenously or intraperitoneally therapeutic activity. (usually paclitaxel) for 6 cycles has been the standard of care for many years [5]. Complete clinical response Frontline Treatment and Recurrence will be achieved for the majority of these patients. Frontline treatment for advanced ovarian cancer However, recurrence rates are high and vary by stage. http://www.jcancer.org Journal of Cancer 2021, Vol. 12 39 Patients with stage III or IV disease have a 70-75% maintenance therapy. Previously this has been largely chance of recurrence within two years of diagnosis [6]. physician choice, as maintenance therapy showed Recurrence can be suspected by the onset of new little improvement and carried significant toxicity. A symptoms or rising CA 125 levels. Patients who recur meta-analysis of 8 trials combining chemotherapy after >6 months from the date of the last platinum regimens, did not show an improvement in OS dose are defined as platinum sensitive and typically (HR=1.03), or PFS (HR=1.06) [10]. In addition, have a response to retreatment with platinum based continued exposure to chemotherapy was associated doublet therapy. Those patients who recur after 12 with cumulative toxicity which carried the potential months have an even better response to retreatment to impact later lines of therapy. However, the recent with platinum based chemotherapy [7]. Determining development of targeted molecular therapies has recurrence early, with attempt to utilize rising CA 125 resulted in greater maintenance therapy options with levels is controversial. In a prospective study of less toxicity and greater therapeutic benefit (Figure 1). patients with elevated CA 125 levels, individuals were randomized to receive treatment immediately, or at Targeted Molecular Therapies symptomatic or clinical relapse. The study found no BRCA1/2 Mutation and PARP Inhibitors survival benefit in patients receiving immediate treatment (25.7 versus 27.1 months) and patients Breast cancer susceptibility genes 1 and 2 reported decreased quality of life therefore treatment (BRCA1, BRCA2) are independent tumor suppressor based on CA 125 levels is not routine [8]. genes (TSG) working in concert to protect the genome Platinum resistant patients are defined as against mutations [11]. The encoded proteins, BRCA1 recurrence <6 months after the last dose of platinum and BRCA2, are largely involved in DNA repair, therapy. These patients are typically treated with where they facilitate homologous recombination (HR) pegylated liposomal doxorubicin, topotecan, and non-homologous end-joining (NHEJ) by gemcitabine, paclitaxel or experimental therapy. stabilizing repair proteins and activating checkpoints These systemic therapies can be considered alone or [11]. Fifteen to 25% of patients with ovarian cancer in combination with bevacizumab. The Aurelia Phase have a germline BRCA1/2 mutation, whereas the other III study investigated the use of bevacizumab with 75-85% are BRCA1/2 wildtype [12]. Because of BRCA’s chemotherapy in platinum resistant ovarian cancer core involvement with DNA repair, a mutation in one [9]. Although the study reported significantly longer or both BRCA genes renders the genome susceptible PFS and ORR compared to single agent to the accumulation of DNA damage. Resultant chemotherapy, results exhibited moderately mutations alter cellular signal pathway activity significant drug related toxicity related to the addition contributing to cancer transformation [11]. of bevacizumab. Consequently, patients with germline BRCA1/2 mutations are at increased risk for multiple cancer Maintenance Therapies types. These include but are not limited to breast, Following initial debulking surgery and ovarian, pancreatic, colorectal, laryngeal, fallopian consolidation chemotherapy, patients who have tube, primary peritoneal, and prostate cancers [13-20]. achieved a complete clinical response may receive However, mutations in BRCA1/2 may initiate as a Figure 1. Currently approved therapies in ovarian cancer maintenance. Platinum therapies function by damaging DNA through the formation of cross-links. PARP inhibitors function by disrupting PARP, a key molecule in the DNA repair complex. This kills tumorous cells by the principle of synthetic lethality in homologous repair deficient patients, such as BRCA-mutant. Taxanes prevent depolymerization of microtubules, thereby disrupting the mitotic spindle’s ability to separate in mitosis. Angiogenesis inhibitors interrupt the interaction of proangiogenic factors with their receptors, effectively halting angiogenesis in the tumor microenvironment. http://www.jcancer.org Journal of Cancer 2021, Vol. 12 40 single cell event. These are somatic mutations PARP inhibitors have been designed to negate containing BRCA1/2 and related gene mutations. One PARP’s role in DNA repair. Molecularly, PARPi study evaluating monocellular blood and tumor compete with NAD+ at the PARP catalytic domain, samples from 343 ovarian patients with blocking PARylation and the subsequent formation of next-generation sequencing (NGS) and an Agilent DNA repair complexes [26, 27]. Therefore, PARPi SureSelect XT gene panel determined that 84.9% of remove an essential component of DNA repair mutations in BRCA1/2 and other predisposition genes pathways, rendering cells susceptible to genomic (ATM, PALB2, RAD15D, FANCM) were germline and damage. Normal cells with functional DNA repair the remainder were somatic [21]. pathways may circumvent PARP inhibition to repair Patients with cancer mutations of BRCA1 and DNA via alternative pathways. In contrast, cells that BRCA2 have shown remarkable sensitivity to recently are deficient in DNA repair will be particularly developed poly(ADP-ribose) polymerase (PARP) sensitive to PARP inhibition, resulting in rapid inhibitors (PARPi). Moreover, PARPi use accumulation of mutations. These highly damaged demonstrates moderate activity in patients with cells will then undergo rapid cell death via apoptosis. BRCA1/2 wildtype tumors and positive homologous This principle, termed “synthetic lethality,” provides recombination deficiency (HRD) above a threshold the logic behind using PARPi in patients with level (dependent on the PARPi)
Load more

Recommended publications
  • Immunotherapy in Various Cancers
    © 2021 JETIR June 2021, Volume 8, Issue 6 www.jetir.org (ISSN-2349-5162) Immunotherapy in various Cancers Nirav Parmar 1st Year MSc Student Department of Biosciences and Bioengineering, IIT- Roorkee India Abstract: Immunotherapy in the metastatic situation has changed the therapeutic landscape for a variety of cancers, including colorectal cancer. Immunotherapy has firmly established itself as a new pillar of cancer treatment in a variety of cancer types, from the metastatic stage to adjuvant and neoadjuvant settings. Immune checkpoint inhibitors have risen to prominence as a treatment option based on a better knowledge of the development of the tumour microenvironment immune cell-cancer cell regulation over time. Immunotherapy has lately appeared as the most potential field of cancer research by increasing effectiveness and reducing side effects, with FDA-approved therapies for more than 10 various tumours and thousands of new clinical studies. Key Words: Immunotherapy, metastasis, immune checkpoint. Introduction: In the late 1800s, William B. Coley, now generally regarded as the founder of immunotherapy, tried to harness the ability of immune system to cure cancer for the first time. Coley began injecting live and attenuated bacteria like Streptococcus pyogenes and Serratia marcescens into over a thousand patients in 1891 in the hopes of causing sepsis and significant immunological and antitumor responses. His bacterium mixture became known as "Coley's toxin" and is the first recorded active cancer immunotherapy treatment [1]. To better understand the processes of new and traditional immunological targets, the relationship between the immune system and tumour cells should be examined. Tumours have developed ways to evade immunological responses.
    [Show full text]
  • Tanibirumab (CUI C3490677) Add to Cart
    5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor
    [Show full text]
  • TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (Egfrt)
    (19) TZZ _T (11) EP 2 496 698 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07K 14/71 (2006.01) C12N 9/12 (2006.01) 09.01.2019 Bulletin 2019/02 (86) International application number: (21) Application number: 10829041.2 PCT/US2010/055329 (22) Date of filing: 03.11.2010 (87) International publication number: WO 2011/056894 (12.05.2011 Gazette 2011/19) (54) TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (EGFRt) FOR TRANSDUCED T CELL SELECTION VERKÜRZTER REZEPTOR FÜR DEN EPIDERMALEN WACHSTUMSFAKTOR-REZEPTOR ZUR AUSWAHL UMGEWANDELTER T-ZELLEN RÉCEPTEUR DU FACTEUR DE CROISSANCE DE L’ÉPIDERME TRONQUÉ (EGFRT) POUR LA SÉLECTION DE LYMPHOCYTES T TRANSDUITS (84) Designated Contracting States: • LI ET AL.: ’Structural basis for inhibition of the AL AT BE BG CH CY CZ DE DK EE ES FI FR GB epidermal growth factor receptor by cetuximab.’ GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO CANCER CELL vol. 7, 2005, pages 301 - 311, PL PT RO RS SE SI SK SM TR XP002508255 • CHAKRAVERTY ET AL.: ’An inflammatory (30) Priority: 03.11.2009 US 257567 P checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral (43) Date of publication of application: tissues.’ JEM vol. 203, no. 8, 2006, pages 2021 - 12.09.2012 Bulletin 2012/37 2031, XP008158914 • POWELL ET AL.: ’Large-Scale Depletion of (73) Proprietor: City of Hope CD25+ Regulatory T Cells from Patient Duarte, CA 91010 (US) Leukapheresis Samples.’ J IMMUNOTHER vol. 28, no.
    [Show full text]
  • Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy
    Journal of Clinical Medicine Review Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy Anne M. Macpherson 1, Simon C. Barry 2, Carmela Ricciardelli 1 and Martin K. Oehler 1,3,* 1 Discipline of Obstetrics and Gynaecology, Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide 5000, Australia; [email protected] (A.M.M.); [email protected] (C.R.) 2 Molecular Immunology, Robinson Research Institute, University of Adelaide, Adelaide 5005, Australia; [email protected] 3 Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide 5000, Australia * Correspondence: [email protected]; Tel.: +61-8-8332-6622 Received: 29 July 2020; Accepted: 3 September 2020; Published: 14 September 2020 Abstract: Recent advances in the understanding of immune function and the interactions with tumour cells have led to the development of various cancer immunotherapies and strategies for specific cancer types. However, despite some stunning successes with some malignancies such as melanomas and lung cancer, most patients receive little or no benefit from immunotherapy, which has been attributed to the tumour microenvironment and immune evasion. Although the US Food and Drug Administration have approved immunotherapies for some cancers, to date, only the anti-angiogenic antibody bevacizumab is approved for the treatment of epithelial ovarian cancer. Immunotherapeutic strategies for ovarian cancer are still
    [Show full text]
  • Maintenance Therapy in Solid Tumors Marie-Anne Smit, MD, MS,1 and John L
    Review Maintenance therapy in solid tumors Marie-Anne Smit, MD, MS,1 and John L. Marshall, MD2 1 Department of Internal Medicine, 2 Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC The concept of maintenance therapy has been well studied in hematologic malignancies, and now, an increasing number of clinical trials explore the role of maintenance therapy in solid cancers. Both biological and lower-intensity chemotherapeutic agents are currently being evaluated as maintenance therapy. However, despite the increase in research in this area, there has not been consensus about the definition and timing of maintenance therapy. In this review, we will focus on continuation maintenance therapy and switch maintenance therapy in patients with metastatic solid tumors who have achieved stable disease, partial response, or complete response after first-line treatment. aintenance therapy is the subject of an apeutic agents, such as capecitabine and oral 5- increased interest in cancer research. fluorouracil (5-FU), are currently being evaluated as MIn contrast to conventional chemo- maintenance therapy. therapy that aims to kill as many cancer cells as Despite the increase in research in this area, possible, the goal of treatment with maintenance there is no consensus on the definition and timing therapy is to sustain a stable tumor mass, reduce of maintenance therapy. The term maintenance cancer-related symptoms, and prolong the time to therapy is used in a variety of treatment situations, progression and the related symptoms. A thera- such as prolonged first-line therapy and less- peutic strategy that is explicitly designed to main- intense or different therapy given after first-line tain a stable, tolerable tumor volume could in- therapy.
    [Show full text]
  • Ovarian Cancer Immunotherapy and Personalized Medicine
    International Journal of Molecular Sciences Review Ovarian Cancer Immunotherapy and Personalized Medicine Susan Morand 1, Monika Devanaboyina 1 , Hannah Staats 1, Laura Stanbery 2 and John Nemunaitis 2,* 1 Department of Medicine, University of Toledo, Toledo, OH 43614, USA; [email protected] (S.M.); [email protected] (M.D.); [email protected] (H.S.) 2 Gradalis, Inc., Carrollton, TX 75006, USA; [email protected] * Correspondence: [email protected] Abstract: Ovarian cancer response to immunotherapy is limited; however, the evaluation of sen- sitive/resistant target treatment subpopulations based on stratification by tumor biomarkers may improve the predictiveness of response to immunotherapy. These markers include tumor mutation burden, PD-L1, tumor-infiltrating lymphocytes, homologous recombination deficiency, and neoanti- gen intratumoral heterogeneity. Future directions in the treatment of ovarian cancer include the utilization of these biomarkers to select ideal candidates. This paper reviews the role of immunother- apy in ovarian cancer as well as novel therapeutics and study designs involving tumor biomarkers that increase the likelihood of success with immunotherapy in ovarian cancer. Keywords: ovarian cancer; immunotherapy; biomarker 1. Introduction Citation: Morand, S.; Devanaboyina, In the United States, 22,000 patients are diagnosed with ovarian cancer annually, M.; Staats, H.; Stanbery, L.; making it the eleventh most common cancer among female patients and the fifth leading Nemunaitis, J. Ovarian Cancer cause of cancer-related death in women [1,2]. Current front-line standard of care includes Immunotherapy and Personalized debulking surgery with platinum–taxane maintenance chemotherapy. Following front-line Medicine. Int. J. Mol. Sci. 2021, 22, therapy, cancer will recur in 60–70% of patients with optimal debulking (<1 cm residual 6532.
    [Show full text]
  • The Two Tontti Tudiul Lui Hi Ha Unit
    THETWO TONTTI USTUDIUL 20170267753A1 LUI HI HA UNIT ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017 /0267753 A1 Ehrenpreis (43 ) Pub . Date : Sep . 21 , 2017 ( 54 ) COMBINATION THERAPY FOR (52 ) U .S . CI. CO - ADMINISTRATION OF MONOCLONAL CPC .. .. CO7K 16 / 241 ( 2013 .01 ) ; A61K 39 / 3955 ANTIBODIES ( 2013 .01 ) ; A61K 31 /4706 ( 2013 .01 ) ; A61K 31 / 165 ( 2013 .01 ) ; CO7K 2317 /21 (2013 . 01 ) ; (71 ) Applicant: Eli D Ehrenpreis , Skokie , IL (US ) CO7K 2317/ 24 ( 2013. 01 ) ; A61K 2039/ 505 ( 2013 .01 ) (72 ) Inventor : Eli D Ehrenpreis, Skokie , IL (US ) (57 ) ABSTRACT Disclosed are methods for enhancing the efficacy of mono (21 ) Appl. No. : 15 /605 ,212 clonal antibody therapy , which entails co - administering a therapeutic monoclonal antibody , or a functional fragment (22 ) Filed : May 25 , 2017 thereof, and an effective amount of colchicine or hydroxy chloroquine , or a combination thereof, to a patient in need Related U . S . Application Data thereof . Also disclosed are methods of prolonging or increasing the time a monoclonal antibody remains in the (63 ) Continuation - in - part of application No . 14 / 947 , 193 , circulation of a patient, which entails co - administering a filed on Nov. 20 , 2015 . therapeutic monoclonal antibody , or a functional fragment ( 60 ) Provisional application No . 62/ 082, 682 , filed on Nov . of the monoclonal antibody , and an effective amount of 21 , 2014 . colchicine or hydroxychloroquine , or a combination thereof, to a patient in need thereof, wherein the time themonoclonal antibody remains in the circulation ( e . g . , blood serum ) of the Publication Classification patient is increased relative to the same regimen of admin (51 ) Int .
    [Show full text]
  • Your Guide to the Latest Cancer Research and Treatments
    HIGHLIGHTS FROM ASCO 2010 Your Guide to the Latest Cancer Research and Treatments Highlights from the 2010 Annual Meeting of the American Society of Clinical Oncology Learn about: • Recent news on various cancers • Promising new treatments • Clinical trials • Managing side effects Help and Hope CancerCare is a national nonprofit organization that provides free professional support services to anyone affected by cancer: people with cancer, caregivers, children, loved ones, and the bereaved. CancerCare programs—including counseling and support groups, education, financial assistance, and practical help—are provided by professional oncology social workers and are completely free of charge. Founded in 1944, CancerCare provided individual help to more than 100,000 people last year, in addition to serving more than 1 million unique visitors to our websites. For more information, call 1-800-813-HOPE (4673) or visit www.cancercare.org. Contacting CancerCare National Office CancerCare 275 Seventh Avenue New York, NY 10001 [email protected] 1-800-813-HOPE (4673) www.cancercare.org If you are a health care professional interested in ordering free copies of this booklet for your patients, please use the online order form on our website, www.cancercare.org. HIGHLIGHTS FROM ASCO 2010 Your Guide to the Latest Cancer Research and Treatments Highlights from the 2010 Annual Meeting of the American Society of Clinical Oncology Presented by: CancerCare Edited by: Kenneth C. Anderson, MD Charles L. Loprinzi, MD Harvard Medical School and Mayo Clinic Dana-Farber Cancer Institute Maurie Markman, MD Henry S. Friedman, MD The University of Texas Duke University Medical Center MD Anderson Cancer Center William J.
    [Show full text]
  • (INN) for Biological and Biotechnological Substances
    INN Working Document 05.179 Update 2013 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) INN Working Document 05.179 Distr.: GENERAL ENGLISH ONLY 2013 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) International Nonproprietary Names (INN) Programme Technologies Standards and Norms (TSN) Regulation of Medicines and other Health Technologies (RHT) Essential Medicines and Health Products (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) © World Health Organization 2013 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int ) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected] ). Requests for permission to reproduce or translate WHO publications – whether for sale or for non-commercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html ). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]
  • Targeted Molecular Therapies for Ovarian Cancer: an Update and Future Perspectives (Review)
    ONCOLOGY REPORTS 28: 395-408, 2012 Targeted molecular therapies for ovarian cancer: An update and future perspectives (Review) HIROSHI SHIGETOMI, YUMI HIGASHIURA, HIROTAKA KAJIHARA and HIROSHI KOBAYASHI Department of Obstetrics and Gynecology, Nara Medical University, Nara 634-8522, Japan Received February 20, 2012; Accepted May 3, 2012 DOI: 10.3892/or.2012.1833 Abstract. Identification of the potential gene expression profiles Advances in surgical and chemotherapeutic management of epithelial ovarian cancer and the arrival of newly targeted have improved progression-free survival (PFS) and overall therapies have advanced the strategies used for treatment of survival (OS) over the past decade. Paclitaxel plus carboplatin this disease. This review focuses on the design of ongoing and combination is the primary treatment strategy in the front- planned clinical trials and offers a synopsis of the English- line setting. Unfortunately, many women eventually relapse language literature for preclinical and clinical targeted therapies after adjuvant therapy, and are at great risk of recurrence. A for epithelial ovarian cancer. Among many targeted agents, a major challenge is to understand the molecular mechanism promising, novel class of targeted drugs for special patient leading to the state of resistance to standard chemotherapy. populations expected to improve the effectiveness of current Novel drugs are being developed to target specific molec- therapy include inhibitors of angiogenesis, poly (ADP ribose) ular pathways (1). Knowledge of the pathogenesis of ovarian polymerase (PARP) and DNA repair mechanisms. Inhibition cancer has led to a better understanding and identification of PARP or homologous recombination (HR) repair mediated of potential molecular targets which hold great promise for by Chk1 (checkpoint kinase 1) would selectively sensitize p53 personalized treatment.
    [Show full text]
  • INN Working Document 05.179 Update 2011
    INN Working Document 05.179 Update 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) INN Working Document 05.179 Distr.: GENERAL ENGLISH ONLY 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Essential Medicines and Pharmaceutical Policies (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) © World Health Organization 2011 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]
  • Therapeutic Antibody
    www.creativebiolabs.net THERAPEUTIC ANTIBODY Tel: 1-631-871-5806 Fax: 1-631-207-8356 45-1 Ramsey Road, Shirley, NY 11967, USA DBA Italia s.r.l. Via Umbria, 10, 20090 Segrate (Milan) Tel: +39 02 26922300 Fax:+39 02 26923535 DBA Italia s.r.l. email: [email protected] Via Umbria, 10, 20090 Segrate (Milan) Tel: +39 02 26922300 Fax:+39 02 26923535 email: [email protected] Products List Creative Biolabs is a pioneer and undisputed global leader in the rapidly emerging market for therapeutic antibodies. We offer a full range of therapeutic antibodies currently available for research of a wide variety of diseases. We guarantee generated endotoxin free antibodies are fully functional and ready to use in animal- based assays and clinical trials. I Autoimmune and Inflammatory Diseases Antibody Cat. No Product Name Related Disease Name/Clone Anti-Human ITGA4+ITGB7 TAB-H02 Abrilumab Ulcerative colitis Therapeutic Antibody Anti-Human TNF Therapeutic Adalimumab Juvenile Idiopathic Arthritis TAB-010 Antibody TAB-717 Anti-APP Therapeutic Antibody Aducanumab Alzheimer's disease Anti-Human SOST Therapeutic Postmenopausal women TAB-115 Antibody Blosozumab osteoporosis Anti-Human IL12+IL23 Briakinumab Crohn's disease TAB-103 Therapeutic Antibody Anti-Human IL17RA Therapeutic Brodalumab Psoriatic arthritis TAB-134 Antibody Anti-Human MCP-1 Therapeutic Carlumab Immune disease TAB-117 Antibody Anti-Human CD4 Therapeutic Cedelizumab Allograft rejection TAB-107 Antibody Anti-Human IL6 Therapeutic TAB-094 Clazakizumab Crohn's disease Antibody Anti-Human CD4 Therapeutic TAB-260 Tregalizumab Psoriasis Antibody Anti-Human ITGA4 Therapeutic TAB-022 Natalizumab Multiple sclerosis Antibody Anti-Human CD11a Therapeutic TAB-108 Odulimomab Allograft rejection Antibody TAB-772 Anti-CD20 Therapeutic Antibody Ocrelizumab Multiple sclerosis Anti-Human IGHE Therapeutic TAB-007 Omalizumab Allergic asthma Antibody Anti-Human IL4 Therapeutic TAB-221 Pascolizumab Allergy Antibody www.creativebiolabs.net 4 / 30 Products List II Cancers Antibody Cat.
    [Show full text]