keyword
MENU ▼
Read by QxMD icon Read
search

CDK4/6 AND cancer

keyword
https://www.readbyqxmd.com/read/28537004/mek-inhibitors-in-the-treatment-of-metastatic-melanoma-and-solid-tumors
#1
REVIEW
Antonio M Grimaldi, Ester Simeone, Lucia Festino, Vito Vanella, Martina Strudel, Paolo A Ascierto
The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines...
May 23, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28533223/monarch-1-a-phase-2-study-of-abemaciclib-a-cdk4-and-cdk6-inhibitor-as-a-single-agent-in-patients-with-refractory-hr-her2-metastatic-breast-cancer
#2
Maura N Dickler, Sara Tolaney, Hope S Rugo, Javier Cortés, Veronique Dieras, Debra A Patt, Hans Wildiers, Clifford A Hudis, Joyce A O'Shaughnessy, Esther Zamora, Denise Yardley, Martin Frenzel, Andrew G Koustenis, José Baselga
<br />The phase 2 MONARCH 1 study was designed to evaluate the single-agent activity and adverse event (AE) profile of abemaciclib, a selective inhibitor of CDK4 and CDK6, in women with refractory hormone receptor positive (HR+), HER2- metastatic breast cancer (MBC). <br /><br />Experimental Design: <br />MONARCH 1 was a phase 2 single arm open-label study. Women with HR+/HER2- MBC who had progressed on or after prior endocrine therapy and had 1 or 2 chemotherapy regimens in the metastatic setting were eligible...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28530853/designing-clinical-trials-that-accept-new-arms-an-example-in-metastatic-breast-cancer
#3
Steffen Ventz, Brian M Alexander, Giovanni Parmigiani, Richard D Gelber, Lorenzo Trippa
Purpose The majority of randomized oncology trials are two-arm studies that test the efficacy of new therapies against a standard of care, thereby assigning a large proportion of patients to nonexperimental therapies. In contrast, multiarm studies efficiently share a common control arm while evaluating multiple experimental therapies. A major bottleneck for traditional multiarm trials is the requirement that all therapies-often drugs from different companies-have to be available at the same time when the trial starts...
May 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28529550/hormonoresistance-in-advanced-breast-cancer-a-new-revolution-in-endocrine-therapy
#4
REVIEW
Paule Augereau, Anne Patsouris, Emmanuelle Bourbouloux, Carole Gourmelon, Sophie Abadie Lacourtoisie, Dominique Berton Rigaud, Patrick Soulié, Jean Sebastien Frenel, Mario Campone
Endocrine therapy is the mainstay of treatment of estrogen-receptor-positive (ER+) breast cancer with an overall survival benefit. However, some adaptive mechanisms in the tumor emerge leading to the development of a resistance to this therapy. A better characterization of this process is needed to overcome this resistance and to develop new tailored therapies. Mechanisms of resistance to hormone therapy result in activation of transduction signal pathways, including the cell cycle regulation with cyclin D/CDK4/6/Rb pathway...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28526299/mir-200a-regulates-cdk4-6-inhibitor-effect-by-targeting-cdk6-in-metastatic-melanoma
#5
Matias A Bustos, Shigeshi Ono, Diego M Marzese, Takashi Oyama, Yuuki Iida, Garrett Cheung, Nellie Nelson, Sandy C Hsu, Qiang Yu, Dave S B Hoon
Cyclin-dependent kinase (CDK) 4 and 6 pathway is frequently dysregulated in cutaneous melanoma. Recently, CDK4/6 inhibitors have shown promising clinical activity against several cancer types, including melanoma. Here, we demonstrate that miR-200a decreases CDK6 expression and thus reduces the response of CDK4/6 inhibitor in highly proliferative metastatic melanoma. Down-regulation of miR-200a expression in melanoma cells is associated with disease progression and a higher number of lymph node metastases. Furthermore, miR-200a expression is epigenetically modulated by both DNA methylation at the promoter region and chromatin accessibility of an upstream genomic region with enhancer activity...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28516152/cdk4-6-inhibitors-in-cancer-therapy-a%C3%A2-novel-treatement-strategy-for-bladder-cancer
#6
REVIEW
Qi Pan, Anuja Sathe, Peter C Black, Peter J Goebell, Ashish M Kamat, Bernd Schmitz-Draeger, Roman Nawroth
Patients with metastatic bladder cancer (mBC) treated with cisplatin-based chemotherapy have a limited median survival of only around 14 months [1]. Despite over 30 years of basic and clinical research, until recently no therapeutic options beyond cisplatin-based therapy had entered clinical routine and, at least in the US, none of the tested agents had been approved for second-line treatment. This has changed with the advent of immune checkpoint blockade, including especially PD-1/PD-L1 inhibitors. The high response rates of 24% over a 14...
April 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/28515242/new-approaches-to-endocrine-therapy-for-breast-cancer
#7
William J Gradishar
The management of advanced hormone receptor-positive disease has evolved with the emergence of CDK4/6 inhibitors. Improvements in progression-free survival of approximately 10 months were noted in pivotal trials of palbociclib. Strong efficacy was also seen with ribociclib, which was recently approved by the FDA. In the adjuvant treatment setting of hormone receptor-positive disease, an important issue for consideration is the duration of endocrine therapy.
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28513565/epidermal-growth-factor-receptor-cell-proliferation-signaling-pathways
#8
REVIEW
Ping Wee, Zhixiang Wang
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation...
May 17, 2017: Cancers
https://www.readbyqxmd.com/read/28488183/palbociclib-a-review-in-hr-positive-her2-negative-advanced-or-metastatic-breast-cancer
#9
REVIEW
Esther S Kim, Lesley J Scott
Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates...
May 9, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28486050/the-cdk4-6-inhibitor-palbociclib-synergizes-with-irinotecan-to-promote-colorectal-cancer-cell-death-under-hypoxia
#10
Jun Zhang, Lanlan Zhou, Shuai Zhao, David T Dicker, Wafik S El-Deiry
Hypoxia is an inherent impediment to cancer therapy. Palbociclib, a highly selective inhibitor for CDK4/6, has been tested in numerous clinical trials and has been approved by the FDA. We previously reported that CDK inhibitors can destabilize HIF1α regardless of the presence of hypoxia and can sensitize tumor cells to TRAIL through dual blockade of CDK1 and GSK3-β. In order to translate this knowledge into a cancer therapeutic strategy, we investigated the therapeutic effects and molecular mechanisms of CDK inhibition against colon cancer cells under normoxia and hypoxia...
May 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28479958/cdk4-6-inhibition-in-breast-cancer-mechanisms-of-response-and-treatment-failure
#11
Ana C Garrido-Castro, Shom Goel
PURPOSE OF REVIEW: To describe the role of D-type cyclins and CDKs 4 and 6 in breast cancer, and to discuss potential biomarkers for sensitivity or resistance to CDK4/6 inhibitors. RECENT FINDINGS: A small number of preclinical and clinical studies have explored potential mechanisms of CDK4/6 inhibitor response and resistance in breast cancer. Putative markers of response include ER-positivity, luminal patterns of gene expression, high cyclin D1 levels, and low p16 levels...
March 2017: Current Breast Cancer Reports
https://www.readbyqxmd.com/read/28459517/effect-of-fanbaicao-herba-potentillae-discoloris-oil-on-the-expression-of-p21-and-cdk4-in-hepg2-cells
#12
Lei Liu, Guang Chen, Baixin Wang, Liping Chen, Shuqiu Wang, Zhixin Liu, Xiaoru Ma, Fangfang Wang, Yanfeng Liang, Jiamei Wu, Zhiwei Yang
OBJECTIVE: To research the anti-cancer mechanism of the Traditional Chinese Medicine Fanbaicao (Herba Potentillae Discoloris) oil in the human hepatoma cell line HepG2. METHODS: Gas chromatography was used to analyze the components of Fanbaicao (Herba Potentillae Discoloris). We tested the inhibitory effect of Fanbaicao (Herba Potentillae Discoloris) oil on the human hepatoma cell line HepG2 in vitro using 3-(4, 5-Dimet hylt hiazol-2-yl)-2,5-dip henyltetrazolium bromide assays...
August 2016: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
https://www.readbyqxmd.com/read/28459468/oncogenic-kras-associated-gene-signature-defines-co-targeting-of-cdk4-6-and-mek-as-a-viable-therapeutic-strategy-in-colorectal-cancer
#13
M Pek, S M J M Yatim, Y Chen, J Li, M Gong, X Jiang, F Zhang, J Zheng, X Wu, Q Yu
Therapeutic strategies against KRAS mutant colorectal cancers are developed using cell line models, which do not accurately represent the transcriptome driven by oncogenic KRAS in tumors. We sought to identify a KRAS-associated gene signature from colorectal tumors to develop a precise treatment strategy. Integrative analysis of quantitative KRAS mutation detection and matched gene expression profiling in 55 CRC bulk tumors was carried out to define a gene signature enriched in CRC tumors with high KRAS mutation...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28454587/emerging-therapies-for-breast-cancer
#14
REVIEW
Xichun Hu, Wei Huang, Minhao Fan
HER2 and CDK4/6 are undoubted two most important biological targets for breast cancer. Anti-HER2 treatments enhance objective response and progression-free survival/disease-free survival as well as overall survival. Three CDK4/6 inhibitors consistently improve objective response and progression-free survival; however, overall survival data are waited. Optimization of chemotherapy and endocrine strategies remains an unmet need. Check point inhibitor-based immunotherapy combined with chemotherapy is a promising field, especially for triple-negative breast cancer...
April 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28453226/palbociclib-induces-activation-of-ampk-and-inhibits-hepatocellular-carcinoma-in-a-cdk4-6-independent-manner
#15
Feng-Shu Hsieh, Yao-Li Chen, Man-Hsin Hung, Pei-Yi Chu, Ming-Hsien Tsai, Li-Ju Chen, Yung-Jen Hsiao, Chih-Ting Shih, Mao-Ju Chang, Tzu-I Chao, Chung-Wai Shiau, Kuen-Feng Chen
Palbociclib, a CDK4/6 inhibitor, has recently been approved for hormone receptor-positive breast cancer patients. The effects of palbociclib as a treatment for other malignancies, including hepatocellular carcinoma (HCC), are of great clinical interest and are under active investigation. Here, we report the effects and a novel mechanism of action of palbociclib in HCC. We found that palbociclib induced both autophagy and apoptosis in HCC cells through a mechanism involving 5' AMP-activated protein kinase (AMPK) activation and protein phosphatase 5 (PP5) inhibition...
April 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28446688/transient-cdk4-6-inhibition-protects-hematopoietic-stem-cells-from-chemotherapy-induced-exhaustion
#16
Shenghui He, Patrick J Roberts, Jessica A Sorrentino, John E Bisi, Hannah Storrie-White, Renger G Tiessen, Karenann M Makhuli, William A Wargin, Henko Tadema, Ewoud-Jan van Hoogdalem, Jay C Strum, Rajesh Malik, Norman E Sharpless
Conventional cytotoxic chemotherapy is highly effective in certain cancers but causes dose-limiting damage to normal proliferating cells, especially hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics causes a long-term hematopoietic compromise ("exhaustion"), which limits the use of chemotherapy and success of cancer therapy. We show that the coadministration of G1T28 (trilaciclib), which is a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a serial 5-fluorouracil treatment model...
April 26, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28444744/dual-cdk4-6-inhibition-by-pd-0332991-induces-apoptosis-and-senescence-in-esophageal-squamous-cell-carcinoma-cells
#17
Liang Chen, Jingxuan Pan
BACKGROUND AND PURPOSE: Aberrant activation of Cyclin D1-CDK4/6-Rb signaling pathway is common in esophageal squamous cell carcinoma (ESCC). PD-0332991, a highly specific inhibitor of CDK4/6, has been showed potent antitumor activity against multiple types of cancer. The purpose of this study was to examine the in vitro and in vivo antineoplastic effect of PD-0332991 against the growth and metastasis in ESCC cells. EXPERIMENTAL APPROACH: Cell viability and synergy between PD-0332991 and 5-fluorouracil/Cisplatin were measured by MTS assay and CalcuSyn software, respectively...
April 25, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28438180/recent-advances-of-highly-selective-cdk4-6-inhibitors-in-breast-cancer
#18
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
#19
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/28418845/preclinical-development-of-g1t38-a-novel-potent-and-selective-inhibitor-of-cyclin-dependent-kinases-4-6-for-use-as-an-oral-antineoplastic-in-patients-with-cdk4-6-sensitive-tumors
#20
John E Bisi, Jessica A Sorrentino, Jamie L Jordan, David D Darr, Patrick J Roberts, Francis X Tavares, Jay C Strum
Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance...
March 15, 2017: Oncotarget
keyword
keyword
78797
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"