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https://www.readbyqxmd.com/read/29672168/rucaparib-a-new-treatment-option-for-ovarian-cancer
#1
Ilaria Sabatucci, Giuseppa Maltese, Stefano Lepori, Elisa Tripodi, Giorgio Bogani, Domenica Lorusso
Approximately 50% of high-grade serous ovarian cancers present a deficiency in the pathways involved in homologous recombination (HR). PARP inhibitors prevent single-strand DNA damage repair and determine a progression of the defect towards double-strand breaks, which results in a process known as 'synthetic lethality'. Areas covered: In this review, the authors discuss the efficacy and toxicity of rucaparib either as a single agent or as a maintenance treatment for ovarian cancer. This includes the NGS Foundation Medicine evaluation of the role of this drug in the treatment algorithm of ovarian cancer...
April 19, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29668451/a-review-on-dna-repair-inhibition-by-parp-inhibitors-in-cancer-therapy
#2
REVIEW
Ashish P Shah, Chhagan N Patel, Dipen K Sureja, Kirtan P Sanghavi
The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority of the cancer therapy cause DNA damage which leads to apoptosis. The cell has natural ability to repair this damage which ultimately leads to development of resistance of drugs. The key enzymes involved in DNA repair process are poly(ADP-ribose) (PAR) and poly(ADP-ribose) polymerases (PARP). Tumor cells repair their defective gene via defective homologues recombination (HR) in the presence of enzyme PARP. PARP inhibitors inhibit the enzyme poly(ADP-ribose) polymerases (PARPs) which lead to apoptosis of cancer cells...
March 1, 2018: Folia Medica
https://www.readbyqxmd.com/read/29660759/parp-inhibitors-in-breast-cancer-bringing-synthetic-lethality-to-the-bedside
#3
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/29616377/male-secretory-breast-cancer-case-in-a-6-year-old-boy-with-a-peculiar-gene-duplication-and-review-of-the-literature
#4
REVIEW
M Ghilli, M D Mariniello, C Scatena, L Dosa, G Traficante, A Tamburini, C Caporalini, A M Buccoliero, F Facchini, L Colizzi, A Quattrini Li, E Landucci, G Manca, A G Naccarato, D Caramella, C Favre, M Roncella
PURPOSE: Secretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms. METHODS: We describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features...
April 3, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29606854/rucaparib-a-novel-parp-inhibitor-for-brca-advanced-ovarian-cancer
#5
REVIEW
Ilaria Colombo, Stephanie Lheureux, Amit Manulal Oza
Rucaparib is a potent small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP) proteins (PARP-1, PARP-2 and PARP-3) that play an important role in repairing DNA damage and maintaining genomic stability. Tumors with mutations in BRCA1/2 or other homologous recombination deficiency (HRD) genes are particularly sensitive to PARP inhibitors because of "synthetic lethality", whereby a therapeutic agent can take advantage of an intrinsic weakness in DNA repair. Rucaparib has been investigated in several preclinical and clinical studies showing promising activity in BRCA -mutant and BRCA -wild-type epithelial ovarian cancers (EOCs)...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29605737/rucaparib-an-emerging-parp-inhibitor-for-treatment-of-recurrent-ovarian-cancer
#6
REVIEW
Angela Musella, Erlisa Bardhi, Claudia Marchetti, Laura Vertechy, Giusy Santangelo, Carolina Sassu, Federica Tomao, Francesco Rech, Renzo D'Amelio, Marco Monti, Innocenza Palaia, Ludovico Muzii, Pierluigi Benedetti Panici
Recently, Poly-ADP-Ribose Polymerase (PARP) inhibitors are one of the most intensively studied group of antiblastic agents for the management of recurrent ovarian cancer. Among this family, Olaparib was the first to be approved by European Medicines Agency as maintenance therapy post-response to platinum-based chemotherapy for recurrent ovarian cancer in women with deleterious BRCA1/2 mutation. Following that, the Food and Drug Administration (FDA) approved Olaparib monotherapy as fourth or later line of treatment in advanced ovarian cancer with deleterious germ-line BRCA1/2 mutation...
March 23, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29597073/p21-activated-kinase-1-nuclear-activity-and-its-role-during-dna-damage-repair
#7
REVIEW
Eloy Andrés Pérez-Yépez, Héctor Iván Saldívar-Cerón, Olga Villamar-Cruz, Carlos Pérez-Plasencia, Luis Enrique Arias-Romero
p21-activated kinase 1 (PAK1) is a serine/threonine kinase activated by the small GTPases Rac1 and Cdc42. It is located in the chromosome 11q13 and is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme plays a pivotal role in the control of a number of fundamental cellular processes by phosphorylating its downstream substrates. In addition to its role in the cytoplasm, it is well documented that PAK1 also plays crucial roles in the nucleus participating in mitotic events and gene expression through its association and/or phosphorylation of several transcription factors, transcriptional co-regulators and cell cycle-related proteins, including Aurora kinase A (AURKA), polo-like kinase 1 (PLK1), the forkhead transcription factor (FKHR), estrogen receptor α (ERα), and Snail...
March 21, 2018: DNA Repair
https://www.readbyqxmd.com/read/29593098/administration-of-the-tablet-formulation-of-olaparib-in-patients-with-ovarian-cancer-practical-guidance-and-expectations
#8
REVIEW
Kathleen N Moore, Michael J Birrer
Olaparib is a poly(ADP-ribose) polymerase enzyme inhibitor that is approved for use in patients with advanced ovarian cancer (OC) and genetic BRCA1/2 mutations who have received three or more prior lines of chemotherapy for maintenance treatment of recurrent OC that is in response to platinum-based chemotherapy regardless of BRCA mutation status and for human epidermal growth receptor factor 2-negative metastatic breast cancer with deleterious or suspected deleterious germline BRCA mutations who have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting...
March 28, 2018: Oncologist
https://www.readbyqxmd.com/read/29582690/olaparib-for-the-treatment-of-breast-cancer
#9
Gaia Griguolo, Maria Vittoria Dieci, Valentina Guarneri, PierFranco Conte
Mutations in BRCA1 and BRCA2 genes account for around 2-3% of breast cancer events and more than 10% of triple negative breast cancers. Olaparib (Lynparza®), an orally administered PARP inhibitor, demonstrated clinical benefit in a phase III trial for mutated BRCA-positive HER2 negative metastatic breast cancer. Areas covered: This review gives an overview of available preclinical and clinical data regarding olaparib, including its chemistry, mechanism of action, pharmacokinetics and pharmacodynamics, and evidence supporting antitumor efficacy and safety profile in breast cancer patients...
March 27, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29521233/parp-inhibitors-for-the-treatment-of-ovarian-cancer
#10
Laura Cortesi, Angela Toss, Iole Cucinotto
The standard of treatment for advanced ovarian cancer is represented by optimal surgical debulking preceded or followed by chemotherapeutic regimens including taxanes and platinum agents, possibly associated with bevacizumab and/or intraperitoneal therapy. Despite this comprehensive treatment strategy, almost 75% of patients relapse or progress and are therefore candidates for a second-line treatment, showing, at this point, less chemo-sensitivity and worse prognosis. An interesting approach to improve outcomes of these patients has been developed in the last decade, in BRCA-related ovarian cancer...
March 7, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29512470/parp-inhibitors-in-ovarian-cancer
#11
Gloria Mittica, Eleonora Ghisoni, Gaia Giannone, Sofia Genta, Massimo Aglietta, Anna Sapino, Giorgio Valabrega
BACKGROUND: Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients. OBJECTIVES: To highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis...
March 5, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29486991/characteristics-of-african-american-women-at-high-risk-for-ovarian-cancer-in-the-southeast-results-from-a-gynecologic-cancer-risk-assessment-clinic
#12
David A Barrington, Macie L Champion, Teresa K L Boitano, Christen L Walters-Haygood, Meagan B Farmer, Ronald D Alvarez, Jacob M Estes, Charles A Leath
OBJECTIVES: Describe patient characteristics in African American (AA) women seen for gynecologic cancer related genetic counseling at a large southeastern comprehensive cancer center. METHODS: We reviewed an IRB approved, prospective observational cohort of patients from a Gynecologic Cancer Risk Assessment Clinic. Data evaluated included personal cancer history, family history, frequency of genetic testing, frequency/type of genetic mutations, and frequency of surgical intervention...
February 24, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29468855/major-clinical-research-advances-in-gynecologic-cancer-in-2017
#13
REVIEW
Dong Hoon Suh, Miseon Kim, Kyung Hun Lee, Keun Yong Eom, Maj Kamille Kjeldsen, Mansoor Raza Mirza, Jae Weon Kim
In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer...
March 2018: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29466291/recommendations-and-choices-for-brca-mutation-carriers-at-risk-for-ovarian-cancer-a-complicated-decision
#14
REVIEW
Kelsey E Lewis, Karen H Lu, Amber M Klimczak, Samuel C Mok
Current ovarian cancer screening guidelines in high-risk women vary according to different organizations. Risk reducing surgery remains the gold standard for definitive treatment in BRCA mutation carriers, but research advancements have created more short-term options for patients to consider. The decisions involved in how a woman manages her BRCA mutation status can cause a great deal of stress and worry due to the imperfect therapy options. The goal of this review was to critically analyze the screening recommendations and alternative options for high-risk ovarian cancer patients and evaluate how these discrepancies and choices affect a woman's management decisions...
February 21, 2018: Cancers
https://www.readbyqxmd.com/read/29459887/role-of-brca-mutations-in-the-modulation-of-response-to-platinum-therapy
#15
REVIEW
Sanghamitra Mylavarapu, Asmita Das, Monideepa Roy
Recent years have seen cancer emerge as one of the leading cause of mortality worldwide with breast cancer being the second most common cause of death among women. Individuals harboring BRCA mutations are at a higher risk of developing breast and/or ovarian cancers. This risk is much greater in the presence of germline mutations. BRCA1 and BRCA2 play crucial role in the DNA damage response and repair pathway, a function that is critical in preserving the integrity of the genome. Mutations that interfere with normal cellular function of BRCA not only lead to onset and progression of cancer but also modulate therapy outcome of treatment with platinum drugs...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29433453/male-brca-mutation-carriers-clinical-characteristics-and-cancer-spectrum
#16
Mohammed Ibrahim, Siddhartha Yadav, Foluso Ogunleye, Dana Zakalik
BACKGROUND: Mutations in BRCA1 and BRCA2 (BRCA1/2) genes are associated with an increased risk of breast and ovarian cancers in women. The cancer characteristics of men with BRCA1/2 mutations are less well studied. This study describes the unique cancer characteristics of male BRCA1/2 mutation carriers at our institution. METHODS: We performed a retrospective chart review on male patients who were seen between January 2004 and December 2014 and tested positive for a BRCA1/2 mutation...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29428039/rationale-for-mastectomy-after-neoadjuvant-chemotherapy
#17
COMPARATIVE STUDY
Lejla Hadzikadic Gusic, Kendall Walsh, Teresa Flippo-Morton, Terry Sarantou, Danielle Boselli, Richard L White
Neoadjuvant chemotherapy (NAC) reduces tumor size, facilitating the use of breast conservation surgery (BCS). However, mastectomy remains the surgical outcome for certain women. The goal of this study was to determine the rationale for mastectomy after NAC, particularly in women eligible for BCS. Retrospective data were reviewed on patients who received NAC between February 2006 and August 2010 at our institution. Demographics and tumor characteristics were compared between patients who received BCS and mastectomy after NAC...
January 1, 2018: American Surgeon
https://www.readbyqxmd.com/read/29409476/germline-brca1-brca2-mutations-among-high-risk-breast-cancer-patients-in-jordan
#18
Hikmat Abdel-Razeq, Amal Al-Omari, Farah Zahran, Banu Arun
BACKGROUND: Breast cancer is the most common malignancy and the leading cause of cancer-related deaths among Jordanian women. With a median age of 50 years at diagnosis, a higher prevalence of hereditary breast cancer may be expected. The objective of this pilot study is to evaluate, for the first time, the contribution of germline mutations in BRCA1/2 to breast cancer among Jordanian patients. METHODS: Jordanian breast cancer women with a selected high risk profile were invited to participate...
February 6, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29402697/impact-of-brca-mutation-status-on-survival-of-women-with-triple-negative-breast-cancer
#19
Siddhartha Yadav, Rand Ladkany, Dhiraj Yadav, Omar Alhalabi, Sinan Khaddam, Daniel Isaac, Paola Yumpo Cardenas, Dana Zakalik
INTRODUCTION: The effect of germline BRCA mutations on the outcomes of patients with triple-negative breast cancer (TNBC) is not well understood. MATERIALS AND METHODS: The present retrospective study included women with newly diagnosed TNBC from January 1, 2004 to December 30, 2013. The demographic and tumor characteristics, genetic testing results, and outcomes were collected by a review of the patients' medical records. The outcomes were compared between the BRCA+ and BRCA- women...
December 30, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29323669/cost-effectiveness-and-comparative-effectiveness-of-cancer-risk-management-strategies-in-brca1-2-mutation-carriers-a-systematic-review
#20
Lara Petelin, Alison H Trainer, Gillian Mitchell, Danny Liew, Paul A James
PurposeTo review the evidence for the effectiveness and cost-effectiveness of cancer risk management interventions for BRCA carriers.MethodsComparative effectiveness and cost-effectiveness analyses were identified by searching scientific and health economic databases. Eligible studies modeled the impact of a cancer risk management intervention in BRCA carriers on life expectancy (LE), cancer incidence, or quality-adjusted life years (QALYs), with or without costs.ResultsTwenty-six economic evaluations and eight comparative effectiveness analyses were included...
January 11, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
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