keyword
MENU ▼
Read by QxMD icon Read
search

Inhibition BRCA

keyword
https://www.readbyqxmd.com/read/29765551/functional-significance-of-co-occurring-mutations-in-pik3ca-and-map3k1-in-breast-cancer
#1
Alvaro Avivar-Valderas, Robert McEwen, Amir Taheri-Ghahfarokhi, Larissa S Carnevalli, Elizabeth L Hardaker, Marcello Maresca, Kevin Hudson, Elizabeth A Harrington, Francisco Cruzalegui
The PI3Kα signaling pathway is frequently hyper-activated in breast cancer (BrCa), as a result of mutations/amplifications in oncogenes (e.g. HER2 ), decreased function in tumor suppressors (e.g. PTEN ) or activating mutations in key components of the pathway. In particular, activating mutations of PIK3CA (~45%) are frequently found in luminal A BrCa samples. Genomic studies have uncovered inactivating mutations in MAP3K1 (13-20%) and MAP2K4 (~8%), two upstream kinases of the JNK apoptotic pathway in luminal A BrCa samples...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29753961/the-role-of-parp-inhibition-in-triple-negative-breast-cancer-unraveling-the-wide-spectrum-of-synthetic-lethality
#2
REVIEW
Marios Papadimitriou, Giannis Mountzios, Christos A Papadimitriou
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers and is characterized by a lack of immunohistochemical expression of estrogen receptors (ER), progesterone receptors (PR) and HER2. TNBC is associated with poor long-term outcomes compared with other breast cancer subtypes. Many of these tumors are also basal-like cancers which are characterized by an aggressive biological behavior with a distant recurrence peak observed early at 3 years following diagnosis. Furthermore, metastatic TNBC bears a dismal prognosis with an average survival of 12 months...
May 2, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29750420/latest-clinical-evidence-and-further-development-of-parp-inhibitors-in-ovarian-cancer
#3
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/29685157/estrogen-induced-mir-196a-elevation-promotes-tumor-growth-and-metastasis-via-targeting-spred1-in-breast-cancer
#4
Cheng-Fei Jiang, Zhu-Mei Shi, Dong-Mei Li, Ying-Chen Qian, Yi Ren, Xiao-Ming Bai, Yun-Xia Xie, Lin Wang, Xin Ge, Wei-Tao Liu, Lin-Lin Zhen, Ling-Zhi Liu, Bing-Hua Jiang
BACKGROUND: Estrogen plays a critical role in breast cancer (BC) progression through estrogen receptor (ER)-mediated gene regulation. Emerging studies suggest that the malignant progress of BC cells is influenced by the cross talk between microRNAs (miRNAs) and ER-α signaling. However, the mechanism and functional linkage between estrogen and miRNAs remain unclear. METHODS: The expression levels of miR-196a and SPRED1 in BC were tested by qRT-PCR in 46 paired BC and adjacent tissues and by the GEO datasets...
April 23, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29668451/a-review-on-dna-repair-inhibition-by-parp-inhibitors-in-cancer-therapy
#5
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/29651367/-lazarus-response-to-olaparib-in-a-virtually-chemonaive-breast-cancer-patient-carrying-gross-brca2-gene-deletion
#6
Vladimir M Moiseyenko, Vyacheslav A Chubenko, Fedor V Moiseyenko, Lyudmila A Zagorskaya, Yuliya A Zaytseva, Nataliya E Gesha, Evgeny N Zykov, Valeriya I Ni, Elena V Preobrazhenskaya, Anna P Sokolenko, Evgeny N Imyanitov
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene...
February 4, 2018: Curēus
https://www.readbyqxmd.com/read/29615458/an-effective-epigenetic-parp-inhibitor-combination-therapy-for-breast-and-ovarian-cancers-independent-of-brca-mutations
#7
Nicholas Pulliam, Fang Fang, Ali R Ozes, Jessica Tang, Adeoluwa Adewuyi, Harold N Keer, John F Lyons, Stephen B Baylin, Daniela Matei, Harikrishna Nakshatri, Feyruz V Rassool, Kathy D Miller, Kenneth P Nephew
PURPOSE: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are primarily effective against BRCA1/2-mutated breast and ovarian cancers but resistance due to reversion of mutated BRCA1/2 and other mechanisms is common. Based on previous reports demonstrating a functional role for DNMT1 in DNA repair (DDR) and our previous studies demonstrating DNMTis ability to resensitize tumors to primary therapies, we hypothesized that combining a DNMTi with PARPi would sensitize PARPi resistant breast and ovarian cancers to PARPi therapy, independent of BRCA status...
April 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29605737/rucaparib-an-emerging-parp-inhibitor-for-treatment-of-recurrent-ovarian-cancer
#8
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/29592899/synthetic-lethality-of-parp-inhibition-and-ionizing-radiation-is-p53-dependent
#9
Steven T Sizemore, Rahman Mohammed, Gina M Sizemore, Somaira Nowsheen, Hao Yu, Michael C Ostrowski, Arnab Chakravarti, Fen Xia
PARP inhibitors (PARPi) are potentially effective therapeutic agents capable of inducing synthetic lethality in tumors with deficiencies in homologous recombination (HR)-mediated DNA repair such as those carrying BRCA1 mutations. However, BRCA mutations are rare, the majority of tumors are proficient in HR repair, and thus most tumors are resistant to PARPi. Previously, we observed that ionizing radiation (IR) initiates cytoplasmic translocation of BRCA1 leading to suppression of HR-mediated DNA repair and induction of synthetic PARPi lethality in wild-type BRCA1 and HR-proficient tumor cells...
March 28, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29545922/mek-inhibition-leads-to-brca2-downregulation-and-sensitization-to-dna-damaging-agents-in-pancreas-and-ovarian-cancer-models
#10
Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29529211/activity-of-hsp90-inhibiton-in-a-metastatic-lung-cancer-patient-with-a-germline-brca1-mutation
#11
Susana Cedrés, Enriqueta Felip, Cristina Cruz, Ana Martinez de Castro, Nuria Pardo, Alejandro Navarro, Alex Martinez-Marti, Jordin Remon, Jorge Zeron-Medina, Judith Balmaña, Alba Llop-Guevara, Josep M Miquel, Irene Sansano, Paolo Nuciforo, Francesco Mancuso, Violeta Serra, Ana Vivancos
Heat shock proteins (HSPs) are molecular chaperones that maintain proteins in their correct conformation to ensure stability and protect carcinoma cells from apoptosis. HSP90 inhibitors (HSP90i) block multiple targets simultaneously, and despite responses in a selected population, no HSP90i have yet been approved. We present a patient with a lung tumor with an exceptional response to cisplatin/gemcitabine in combination with HSP90i, which nowadays continues with HSP90i maintenance after three years. Whole-exome sequencing of the lung tumor unveiled a BRCA1/2 deficiency mutational signature, and mutation analysis confirmed a germline BRCA1 mutation...
February 26, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29521233/parp-inhibitors-for-the-treatment-of-ovarian-cancer
#12
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/29514732/erratum
#13
Enrico Mini, Ida Landini, Laura Lucarini, Andrea Lapucci, Cristina Napoli, Gabriele Perrone, Renato Tassi, Emanuela Masini, Flavio Moroni, Stefania Nobili
The poly(ADP-ribose) polymerase (PARP) enzymes play a key role in the regulation of cellular processes (e.g., DNA damage repair, genomic stability). It has been shown that PARP inhibitors (PARPIs) are selectively cytotoxic against cells having dysfunctions in genes involved in DNA repair mechanisms (synthetic lethality). Drug-induced PARP inhibition potentiates the activity of anticancer drugs such as 5-fluorouracil in enhancing DNA damage, whose repair involves PARP-1 activity. The aim of this study was to evaluate the inhibitory effects of a novel PARPI, HYDAMTIQ, on growth in human tumor cell lines characterized by different features with regard to DNA damage response pathways (BRCA mutational status, microsatellite status, and ATM expression level) and degree of sensitivity/resistance to 5-fluorouracil...
March 5, 2018: Oncology Research
https://www.readbyqxmd.com/read/29511347/parp-1-inhibition-with-or-without-ionizing-radiation-confers-reactive-oxygen-species-mediated-cytotoxicity-preferentially-to-cancer-cells-with-mutant-tp53
#14
Qi Liu, Liliana Gheorghiu, Michael Drumm, Rebecca Clayman, Alec Eidelman, Matthew F Wszolek, Aria Olumi, Adam Feldman, Meng Wang, Lynnette Marcar, Deborah E Citrin, Chin-Lee Wu, Cyril H Benes, Jason A Efstathiou, Henning Willers
Biomarkers and mechanisms of poly (ADP-ribose) polymerase (PARP) inhibitor-mediated cytotoxicity in tumor cells lacking a BRCA-mutant or BRCA-like phenotype are poorly defined. We sought to explore the utility of PARP-1 inhibitor (PARPi) treatment with/without ionizing radiation in muscle-invasive bladder cancer (MIBC), which has poor therapeutic outcomes. We assessed the DNA damaging and cytotoxic effects of the PARPi olaparib in nine bladder cancer cell lines. Olaparib radiosensitized all cell lines with dose enhancement factors from 1...
March 7, 2018: Oncogene
https://www.readbyqxmd.com/read/29479816/parp-inhibitor-olaparib-sensitizes-cholangiocarcinoma-cells-to-radiation
#15
Yize Mao, Xin Huang, Zeyu Shuang, Guohe Lin, Jun Wang, Fangting Duan, Jianlin Chen, Shengping Li
Cholangiocarcinoma (CCA) is a highly malignant tumor with resistance to radiotherapy alone. Olaparib, a highly potent poly(ADP-ribose) polymerase (PARP) inhibitor, has been shown to sensitize many types of tumor to radiotherapy. However, the effect of olaparib, either as monotherapy or as combination therapy with radiotherapy, on CCA is not known, and our study aimed to explore this. To assess radiosensitization in three CCA cell lines (QBC939, HuH28 and TFK-1), viability and clonogenic assays were conducted...
April 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29397193/the-poly-adp-ribose-polymerase-inhibitor-niraparib-management-of-toxicities
#16
REVIEW
Kathleen N Moore, Mansoor Raza Mirza, Ursula A Matulonis
Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is currently approved by the United States Food and Drug Administration (US FDA) as well as recently approved by the European Medicines Agency (EMA) for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy. The mechanisms of action of niraparib include inhibition of PARP enzymatic activity as well as increased formation of PARP-DNA complexes through "trapping" the PARP enzyme on damaged DNA...
April 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29340034/prexasertib-a-cell-cycle-checkpoint-kinases-1-and-2-inhibitor-increases-in-vitro-toxicity-of-parp-inhibition-by-preventing-rad51-foci-formation-in-brca-wild-type-high-grade-serous-ovarian-cancer
#17
Ethan Brill, Takuhei Yokoyama, Jayakumar Nair, Minshu Yu, Yeong-Ran Ahn, Jung-Min Lee
PARP inhibitors (PARPi) have been effective in high-grade serous ovarian cancer (HGSOC), although clinical activity is limited against BRCA wild type HGSOC. The nearly universal loss of normal p53 regulation in HGSOCs causes dysfunction in the G1/S checkpoint, making tumor cells reliant on Chk1-mediated G2/M cell cycle arrest for DNA repair. Therefore, Chk1 is a reasonable target for a combination strategy with PARPi in treating BRCA wild type HGSOC. Here we investigated the combination of prexasertib mesylate monohydrate (LY2606368), a Chk1 and Chk2 inhibitor, and a PARP inhibitor, olaparib, in HGSOC cell lines (OVCAR3, OV90, PEO1 and PEO4) using clinically attainable concentrations...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29262321/bet-bromodomain-inhibition-synergizes-with-parp-inhibitor-in-epithelial-ovarian-cancer
#18
Sergey Karakashev, Hengrui Zhu, Yuhki Yokoyama, Bo Zhao, Nail Fatkhutdinov, Andrew V Kossenkov, Andrew J Wilson, Fiona Simpkins, David Speicher, Dineo Khabele, Benjamin G Bitler, Rugang Zhang
PARP inhibition is known to be an effective clinical strategy in BRCA mutant cancers, but PARP inhibition has not been applied to BRCA-proficient tumors. Here, we show the synergy of BET bromodomain inhibition with PARP inhibition in BRCA-proficient ovarian cancers due to mitotic catastrophe. Treatment of BRCA-proficient ovarian cancer cells with the BET inhibitor JQ1 downregulated the G2-M cell-cycle checkpoint regulator WEE1 and the DNA-damage response factor TOPBP1. Combining PARP inhibitor Olaparib with the BET inhibitor, we observed a synergistic increase in DNA damage and checkpoint defects, which allowed cells to enter mitosis despite the accumulation of DNA damage, ultimately causing mitotic catastrophe...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29260919/the-development-of-parp-as-a-successful-target-for-cancer-therapy
#19
Roberto Ferrara, Francesca Simionato, Chiara Ciccarese, Elisabetta Grego, Sara Cingarlini, Roberto Iacovelli, Emilio Bria, Giampaolo Tortora, Davide Melisi
PARP1 and BRCA genes are essential genome caretakers and their interaction has been the first example of synthetic lethality, a genetic concept proposed in the early 20th century, but deeply explored in cancer patients only in the last decade. Areas covered: This review describes PARP1 and BRCA main functions and different roles in genome protection. Furthermore, an overview of the principle mechanisms of action and resistance to PARP inhibitors (PARPi) is presented. This review illustrates the concept of BRCAness, and how this discovery has broadened the routes of PARPi to several different malignancies such as ovarian, breast and prostate cancer...
February 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#20
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA -mutant ovarian cancer...
2017: OncoTargets and Therapy
keyword
keyword
26592
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"