keyword
MENU ▼
Read by QxMD icon Read
search

Cdk 4/6

keyword
https://www.readbyqxmd.com/read/28438180/recent-advances-of-highly-selective-cdk4-6-inhibitors-in-breast-cancer
#1
REVIEW
Hanxiao Xu, Shengnan Yu, Qian Liu, Xun Yuan, Sridhar Mani, Richard G Pestell, Kongming Wu
Uncontrolled cell division is the hallmark of cancers. Full understanding of cell cycle regulation would contribute to promising cancer therapies. In particular, cyclin-dependent kinases 4/6 (CDK4/6), which are pivotal drivers of cell proliferation by combination with cyclin D, draw more and more attention. Subsequently, extensive studies were carried out to explore drugs inhibiting CDK4/6 and assess the efficacy and safety of these drugs in cancer, especially breast cancer. Due to the insuperable adverse events and the less activity observed in vivo, the drug development of the initial pan-CDK inhibitor flavopiridol was consequently discontinued, and then highly specific inhibitors were extensively researched and developed, including palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219)...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28432176/a-phase-i-study-of-the-cdk4-6-inhibitor-ribociclib-lee011-in-pediatric-patients-with-malignant-rhabdoid-tumors-neuroblastoma-and-other-solid-tumors
#2
Birgit Geoerger, Franck Bourdeaut, Steven G DuBois, Matthias Fischer, James I Geller, Nicholas G Gottardo, Aurélien Marabelle, Andrew D J Pearson, Shakeel Modak, Thomas Cash, Giles W Robinson, Marlyane Motta, Alessandro Matano, Suraj G Bhansali, Jason R Dobson, Sudha Parasuraman, Susan N Chi
Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off)...
April 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28417244/ribociclib-first-global-approval
#3
Yahiya Y Syed
Ribociclib is an oral, small-molecule inhibitor of cyclin-dependent kinase (CDK) 4 and 6 that is under development by Novartis for the treatment of cancer. CDKs play an important role in cell cycle progression and cellular proliferation, and inhibition of these kinases with ribociclib results in G1 phase cell-cycle arrest. Ribociclib, in combination with an aromatase inhibitor, was recently approved in the USA for the first-line treatment of advanced breast cancer and has been submitted for approval in the EU for this indication...
May 2017: Drugs
https://www.readbyqxmd.com/read/28398051/sesquiterpene-quinones-hydroquinones-from-the-marine-sponge-spongia-pertusa-esper
#4
Jing Li, Bin-Bin Gu, Fan Sun, Jian-Rong Xu, Wei-Hua Jiao, Hao-Bing Yu, Bing-Nan Han, Fan Yang, Xi-Chun Zhang, Hou-Wen Lin
Nine new sesquiterpene quinones/hydroquinones (1-7, 10, and 12), three solvent-generated artifacts (8, 9, and 11), and three known compounds, 5-epi-smenospongine (13), smenospongine (14), and smenospongiadine (15), were isolated from the marine sponge Spongia pertusa Esper. The planar structures of the new compounds were elucidated on the basis of spectroscopic analyses. Their absolute configurations were determined by comparison between the calculated and experimental ECD spectra. In the cytotoxicity bioassay, compounds 13-15 exhibited activities against the human cancer cell lines U937, HeLa, and HepG2, with most potent cytotoxicities to U937 cells with IC50 values of 2...
April 11, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28395543/pharmacokinetic-drug-evaluation-of-ribociclib-for-the-treatment-of-metastatic-hormone-positive-breast-cancer
#5
Giuseppe Curigliano, Carmen Criscitiello, Angela Esposito, Mattia Intra, Saverio Minucci
Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). Ribociclib is an orally bioavailable, highly selective small molecule inhibitor of CDK4/6 that induces G1 arrest at sub-micromolar concentrations in a variety of pRb-positive cancer cells in vitro. Ribociclib is a new standard of care for metastatic HR+/HER2 negative metastatic breast cancer. Area covered: In this article, we review the preclinical and clinical development of ribociclib as well as discussing the role for novel applications of these agents outside the arena of HR-positive, HER2-negative advanced breast cancer...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28359238/hr-her2-advanced-breast-cancer-and-cdk4-6-inhibitors-mode-of-action-clinical-activity-and-safety-profiles
#6
Sarah L Sammons, Donna L Topping, Kimberly L Blackwell
Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapies have shown great promise in improving clinical outcomes for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Addition of a CDK4/6 inhibitor to endocrine therapy increases efficacy and delays disease progression. Successful use of CDK4/6 inhibitor-based therapies in the clinic requires insight into the unique side-effect profiles of this class of agents and effective patient monitoring...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28356261/ribociclib-approved-for-advanced-breast-cancer
#7
(no author information available yet)
The FDA has approved ribociclib combined with aromatase inhibitor therapy for women with metastatic HR-positive, HER2-negative breast cancer. It is the second CDK 4/6 inhibitor approved for these patients, behind palbociclib; a third is under investigation.
March 29, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28351928/ribociclib-lee011-mechanism-of-action-and-clinical-impact-of-this-selective-cyclin-dependent-kinase-4-6-inhibitor-in-various-solid-tumors
#8
Debu Tripathy, Aditya Bardia, William R Sellers
The cyclin D-cyclin-dependent kinase (CDK) 4/6-p16-retinoblastoma (Rb) pathway is commonly disrupted in cancer, leading to abnormal cell proliferation. Therapeutics targeting this pathway have demonstrated antitumor effects in preclinical and clinical studies. Ribociclib is a selective, orally bioavailable inhibitor of CDK4 and CDK6, which was granted priority review by the US Food and Drug Administration in November 2016, and is set to enter the treatment landscape alongside other CDK4/6 inhibitors, including palbociclib and abemaciclib...
March 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28323486/enterolactone-induces-g1-phase-cell-cycle-arrest-in-nonsmall-cell-lung-cancer-cells-by-downregulating-cyclins-and-cyclin-dependent-kinases
#9
Shireen Chikara, Kaitlin Lindsey, Harsharan Dhillon, Sujan Mamidi, Jeffrey Kittilson, Melpo Christofidou-Solomidou, Katie M Reindl
Flaxseed is a rich source of the plant lignan secoisolariciresinol diglucoside (SDG), which is metabolized into mammalian lignans enterodiol (ED) and enterolactone (EL) in the digestive tract. The anticancer properties of these lignans have been demonstrated for various cancer types, but have not been studied for lung cancer. In this study, we investigated the anticancer effects of EL for several nonsmall cell lung cancer (NSCLC) cell lines of various genetic backgrounds. EL inhibited the growth of A549, H441, and H520 lung cancer cells in concentration- and time-dependent manners...
March 21, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28316571/anti-cancerous-potential-of-polysaccharide-fractions-extracted-from-peony-seed-dreg-on-various-human-cancer-cell-lines-via-cell-cycle-arrest-and-apoptosis
#10
Fang Zhang, Jun-Jun Shi, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Zhao-Jun Wei
In this study, four homo/heterogenous polysaccharides (HBSS, CHSS, DASS, and CASS) extracted from peony seed dreg with respective molecular weights of 3467, 4677, 229, and 56 kDa were evaluated for anti-cancerous attributes in prostate cancer cells (Pc-3), colon cancer cells (HCT-116), human breast cancer cells (MCF-7), cervical cancer (Hela cells) and human embryonic kidney 293 (HEK 293) cells as control. Among them, CASS and DASS extracted by alkali, consisted of 34.43% Gal, 26.39% Ara, 21.80% Glc and 35...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28278134/limited-open-quadriceps-release-for-treatment-of-congenital-dislocation-of-the-knee
#11
Ahmed Omar Youssef
BACKGROUND: Congenital dislocation of the knee (CDK) is a rare condition for which the treatment is difficult and remains controversial. The aim of this case series is to evaluate the results of limited open quadriceps release for treatment of CDK. METHODS: Sixteen patients with CDK were managed at our institute from May 2006 to May 2014, and included 10 boys and 6 girls, with a mean age at presentation of 5 weeks (range, 1 to16 wk). Three patients who had an underlying neuromuscular syndrome were excluded...
April 2017: Journal of Pediatric Orthopedics
https://www.readbyqxmd.com/read/28270497/neopalana-neoadjuvant-palbociclib-a-cyclin-dependent-kinase-4-6-inhibitor-and-anastrozole-for-clinical-stage-2-or-3-estrogen-receptor-positive-breast-cancer
#12
Cynthia X Ma, Feng Gao, Jingqin Luo, Donald W Northfelt, Matthew P Goetz, Andres Forero, Jeremy Hoog, Michael J Naughton, Foluso Ademuyiwa, Rama Suresh, Karen S Anderson, Julie Margenthaler, Rebecca Aft, Timothy J Hobday, Timothy Moynihan, William Gillanders, Amy Cyr, Timothy J Eberlein, Tina Hieken, Helen Krontiras, Zhanfang Guo, Michelle Lee, Nicholas C Spies, Zachary L Skidmore, Obi L Griffith, Malachi Griffith, Shana Thomas, Caroline Bumb, Kiran Vij, Cynthia Huang Bartlett, Maria Koehler, Hussam Al-Kateb, Souzan Sanati, Matthew J Ellis
PURPOSE: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. EXPERIMENTAL DESIGN: Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28168733/a-case-of-linear-basal-cell-carcinoma-evaluation-of-proliferative-activity-by-immunohistochemical-staining-of-pctaire1-and-p27
#13
LETTER
Y Yamaguchi, T Yanagi, K Imafuku, S Kitamura, H Hata, H Nishihara, H Shimizu
No abstract text is available yet for this article.
February 6, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28160858/erythro-austrobailignan-6-down-regulates-her2-egfr-integrin%C3%AE-3-expression-via-p38-activation-in-breast-cancer
#14
Jae-Hyun Han, Ha Jin Jeong, Han Na Lee, Yun Ju Kwon, Heung-Mook Shin, Yura Choi, Seongmi Lee, Seung Tack Oh, Dong-Il Kim, Songhee Jeon
BACKGROUND: Despite the benefits from different options of therapy for breast cancer, resistance of the disease to these therapies is rising and a novel agent is needed. Erythro-austrobailignan-6 (EA6) exhibits anti-cancer activity. However, the detailed anti-tumor mechanisms by which EA6 inhibits 4T-1 and MCF-7 cell growth have not been well studied. PURPOSE: In this study, we investigated the anti-proliferative and anti-tumor properties of EA6 on breast carcinoma and its accompanying mechanisms...
January 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28126188/-cell-cycle-inhibitors-in-endocrine-receptor-positive-breast-cancer
#15
Marie-Paule Sablin, Francesco Ricci, Delphine Loirat, Aude Jobard, Clémence Basse, Emanuela Romano, Christophe Le Tourneau, Véronique Dieras
Dysregulation of cellular cycle is a key component of carcinogenesis and its targeting represents an interesting approach. Recently, the development of selective inhibitors of the cycle targeting the cyclin-dependent kinases (CDK) 4 and 6 revived interest in this therapeutic class after the failure of pan-inhibitors. Palbociclib, ribociclib, and abemaciclib are the 3 drugs with the most advanced development. They demonstrated preclinical activity in luminal breast cancer models and are under clinical evaluation...
February 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#16
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28053959/sorbus-rufopilosa-extract-exhibits-antioxidant-and-anticancer-activities-by-inducing-cell-cycle-arrest-and-apoptosis-in-human-colon-adenocarcinoma-ht29-cells
#17
You Na Oh, Soojung Jin, Hyun-Jin Park, Hyun Ju Kwon, Byung Woo Kim
BACKGROUND: Sorbus rufopilosa, a tsema rowan, is a species of the small ornamental trees in the genus Sorbus and the family Rosaceae found in East Asia. The bioactivities of S. rufopilosa have not yet been fully determined. The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. METHODS: To examine the antioxidant activity of EESR, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay was performed...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28005359/cyclin-dependent-kinase-cdk-inhibitors-structure-activity-relationships-and-insights-into-the-cdk-2-selectivity-of-6-substituted-2-arylaminopurines
#18
Christopher R Coxon, Elizabeth Anscombe, Suzannah J Harnor, Mathew P Martin, Benoit Carbain, Bernard T Golding, Ian R Hardcastle, Lisa K Harlow, Svitlana Korolchuk, Christopher J Matheson, David R Newell, Martin E M Noble, Mangaleswaran Sivaprakasam, Susan J Tudhope, David M Turner, Lan Z Wang, Stephen R Wedge, Christopher Wong, Roger J Griffin, Jane A Endicott, Céline Cano
Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 4-((6-([1,1'-biphenyl]-3-yl)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0...
March 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27986745/dual-alk-and-cdk4-6-inhibition-demonstrates-synergy-against-neuroblastoma
#19
Andrew C Wood, Kateryna Krytska, Hannah T Ryles, Nicole R Infarinato, Renata Sano, Theodore D Hansel, Lori S Hart, Frederick J King, Timothy R Smith, Edward Ainscow, Kathryn B Grandinetti, Tove Tuntland, Sunkyu Kim, Giordano Caponigro, You Qun He, Shiva Krupa, Nanxin Li, Jennifer L Harris, Yaël P Mossé
Purpose: Anaplastic lymphoma kinase (ALK) is the most frequently mutated oncogene in the pediatric cancer neuroblastoma. We performed an in vitro screen for synergistic drug combinations that target neuroblastomas with mutations in ALK to determine whether drug combinations could enhance antitumor efficacy.Experimental Design: We screened combinations of eight molecularly targeted agents against 17 comprehensively characterized human neuroblastoma-derived cell lines. We investigated the combination of ceritinib and ribociclib on in vitro proliferation, cell cycle, viability, caspase activation, and the cyclin D/CDK4/CDK6/RB and pALK signaling networks in cell lines with representative ALK status...
December 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27977463/breast-cancer-updates-and-advances-in-2016
#20
Sara B Giordano, William Gradishar
PURPOSE OF REVIEW: Approximately 1 in 8 US women (12%) will develop invasive breast cancer over the course of her lifetime. In 2016, an estimated 246,660 new cases of invasive breast cancer are expected to be diagnosed and approximately 40,450 would die as a result of it. The global burden of breast cancer exceeds all other cancers and the incidence is increasing. The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. This review focuses on the recent advances in breast cancer therapy including hormonal treatment of metastatic breast cancer, targeting cyclin-dependent kinases (CDK) 4/6 in breast cancer, updates in targeting human epidermal growth factor receptor 2 (HER2) positive breast cancer, adaptive randomization trial design and cancer genetic risk assessment...
February 2017: Current Opinion in Obstetrics & Gynecology
keyword
keyword
37193
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"