keyword
MENU ▼
Read by QxMD icon Read
search

CDk4/6 and Breast

keyword
https://www.readbyqxmd.com/read/29772457/in-vitro-and-in-vivo-metabolic-investigation-of-the-palbociclib-by-uhplc-q-tof-ms-ms-and-in-silico-toxicity-studies-of-its-metabolites
#1
Balasaheb B Chavan, Shristy Tiwari, Shankar G, Rakesh D Nimbalkar, Prabha Garg, Srinivas R, M V N Kumar Talluri
Palbociclib (PAB) is a CDK4/6 inhibitor and U. S Food and Drug Administration (FDA) granted regular approval for the treatment of hormone receptor (HR) positive, metastatic breast cancer in combination with an aromatase inhibitor in postmenopausal women. Metabolite identification is a crucial aspect during drug discovery and development as the drug metabolites may be pharmacologically active or possess toxicological activity. As there are no reports on the metabolism studies of the PAB, the present study focused on investigation of the in vitro and in vivo metabolic fate of the drug...
May 14, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29768351/the-cdk4-6-inhibitor-in-hr-positive-advanced-breast-cancer-a-systematic-review-and-meta-analysis
#2
Wu Ding, Zhian Li, Caiyun Wang, GuoDong Ruan, LuPing Chen, Chuanjian Tu
BACKGROUND: Recently, several high-quality clinical randomized controlled trials (RCTs) have identified that cyclin-dependent kinases (CDKs) 4/6 inhibitors obtained a great safety and efficacy, which can be consequently applied as a combination therapy with letrozole or fulvestrant for women who had advanced breast cancer and progressed while receiving endocrine therapy. In this systemic review, we performed a meta-analysis to explore whether CDK4/6 inhibitors had a significantly benefit to treating hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2 negative (HER2-negative) advanced breast cancer...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29763779/clinical-implications-of-the-non-luminal-intrinsic-subtypes-in-hormone-receptor-positive-breast-cancer
#3
REVIEW
Juan Miguel Cejalvo, Tomás Pascual, Aranzazu Fernández-Martínez, Fara Brasó-Maristany, Roger R Gomis, Charles M Perou, Montserrat Muñoz, Aleix Prat
Gene expression profiling has had a considerable impact on our understanding ofbreastcancer biology. Duringthelast decade, 4 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched [HER2-E] and Basal-like) have been identified and intensively studied. In this article, we review and discuss the clinical implications of the 2 non-luminal subtypes (i.e. HER2-E and Basal-like) identified within hormone receptor (HR)-positive disease. After reviewing 32 studies for a total of 13,091 samples, ∼8% and ∼ 15% of early and metastatic HR+/HER2-negative breast cancer, respectively, were found to be non-luminal...
May 7, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29743141/chemotherapy-patient-with-stevens-johnson-syndrome-presents-to-the-emergency-department-a-case-report
#4
Stephanie Widmer, Michele Grossman
BACKGROUND: Stevens-Johnson syndrome (SJS) is part of a continuum of severe mucocutaneous reactions, commonly thought to be triggered by certain medications. The syndrome itself is characterized by diffuse necrosis and detachment of the epidermis. CASE REPORT: This case report discusses a patient who presented to the Emergency Department with signs and symptoms of Stevens-Johnson syndrome four days after chemotherapy administration of ribociclib (Kisqali®). Ribociclib is a newly approved, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor indicated for the treatment of hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer...
April 11, 2018: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29739788/mapk-reliance-via-acquired-cdk4-6-inhibitor-resistance-in-cancer
#5
Renee de Leeuw, Christopher McNair, Matthew J Schiewer, Neermala P Neupane, Lucas J Brand, Michael A Augello, Zhen Li, Larry C Cheng, Akihiro Yoshida, Sean M Courtney, Starr Hazard, Gerald Hardiman, Maha Hussain, J Alan Diehl, Justin M Drake, William K Kelly, Karen E Knudsen
PURPOSE: Loss of cell cycle control is a hallmark of cancer, which can be targeted with agents, including Cyclin Dependent Kinase-4/6 (CDK4/6) kinase inhibitors that impinge upon the G1-S cell cycle checkpoint via maintaining activity of the retinoblastoma tumor suppressor (RB). This class of drugs is under clinical investigation for various solid tumor types, and has recently been FDA-approved for treatment of breast cancer. However, development of therapeutic resistance is not uncommon...
May 8, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29731395/cdk4-6-inhibitors-the-mechanism-of-action-may-not-be-as-simple-as-once-thought
#6
REVIEW
Mary E Klein, Marta Kovatcheva, Lara E Davis, William D Tap, Andrew Koff
CDK4/6 inhibitors are among a new generation of therapeutics. Building upon the striking success of the combination of CDK4/6 inhibitors and the hormone receptor antagonist letrozole in breast cancer, many other combinations have recently entered clinical trials in multiple diseases. To achieve maximal benefit with CDK4/6 inhibitors it will be critical to understand the cellular mechanisms by which they act. Here we highlight the mechanisms by which CDK4/6 inhibitors can exert their anti-tumor activities beyond simply enforcing cytostatic growth arrest, and discuss how this knowledge may inform new combinations, improve outcomes, and modify dosing schedules in the future...
April 10, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29729292/cyclin-e-overexpression-confers-resistance-to-the-cdk4-6-specific-inhibitor-palbociclib-in-gastric-cancer-cells
#7
Ahrum Min, Jung Eun Kim, Yu-Jin Kim, Jee Min Lim, Seongyeong Kim, Jin Won Kim, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im
Palbociclib is a specific inhibitor of CDK4/6 and has been shown to provide a survival benefit in hormone receptor-positive advanced breast cancer. TCGA database reported that about half of gastric cancers exhibit abnormalities in cell-cycle-related molecules, suggesting that gastric cancer is a good candidate for palbociclib treatment; however, the antitumor effects and predictive markers of palbociclib in gastric cancer remain incompletely described. Herein, the effect and predictive markers of palbociclib on gastric cancer cells were investigated...
May 2, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29725889/use-of-cyclin-dependent-kinase-cdk-4-6-inhibitors-for-hormone-receptor-positive-human-epidermal-growth-factor-receptor-2-negative-metastatic-breast-cancer-a-roundtable-discussion-by-the-breast-cancer-therapy-expert-group-bcteg
#8
REVIEW
Jame Abraham, Robert Coleman, Anthony Elias, Frankie Ann Holmes, Kevin Kalinsky, Muaiad Kittaneh, Elyse Lower, Reshma Mahtani, E Terry Mamounas, Mark Pegram, Charles Vogel
PURPOSE: To provide an overview of clinical data supporting the use of cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (mBC), from the perspective of the practicing oncologist community. METHODS: A recent roundtable discussion was convened by The Breast Cancer Therapy Expert Group (BCTEG) to review existing data on this topic and its impact on their current practice...
May 4, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29700711/cyclin-dependent-kinase-4-6-inhibitors-in-hormone-receptor-positive-early-breast-cancer-preliminary-results-and-ongoing-studies
#9
REVIEW
Dorota Kwapisz
The cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitors (CDK4/6i) induce cell cycle arrest in the G1 phase what eventually can prevent the proliferation of cancer cells. The CDK4/6i have changed the landscape of treatment options for ER-positive, HER2-negative metastatic breast cancer. Currently, palbociclib, ribociclib, and abemaciclib are approved by the US Food and Drug Administration in this setting. This success encouraged the researchers to examine CDK4/6i activity in (neo)adjuvant setting. In this review, clinical data to date and ongoing clinical trials with palbociclib, ribociclib, and abemaciclib in the early breast cancer are discussed...
April 26, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29674428/optimising-endocrine-therapy-in-postmenopausal-women-with-advanced-breast-cancer
#10
Thomas Ho Lai Yau, Kl Cheung
Hormone receptor-positive breast cancer is commonly treated with endocrine therapy; however, overtime cancer cells can develop endocrine resistance. This review aims to document combination therapy and sequential therapy in the use of endocrine agents and targeted agents. By conducting two systematic searches using 4 databases: Cochrane Library, MEDLINE, EMBASE, and Web of Science. A total of 26 studies that covered combination therapy were obtained and included for the review. 14 were phase III documenting combinations of mechanistic target of rapamycin (mTOR), phosphoinositide-3-kinase (PI3K), vascular endothelial growth factor receptor (VEGFR), human epidermal growth factor receptor 2 (HER2), and cyclin dependent kinase 4/6 (CDK4/6) inhibitors...
April 19, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29670855/current-therapies-for-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer-patients
#11
REVIEW
Alexey A Larionov
The median survival of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) has more than doubled, since the discovery of HER2-targeted treatments: it rose from less than 2 years in 2001 (prior introduction of trastuzumab) to more than 4 years in 2017. The initial generation of HER2-targeted therapies included trastuzumab with taxanes in the first line, followed by the addition of lapatinib and by a switch to another cytotoxic agent after progression. Results of CLEOPATRA, EMILIA, and TH3RESA trials have changed this clinical practice...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29670090/inhibition-of-cyclin-dependent-kinase-4-as-a-potential-therapeutic-strategy-for-treatment-of-synovial-sarcoma
#12
Xiaoyang Li, Nicole A Seebacher, Cassandra Garbutt, Hangzhan Ma, Peng Gao, Tao Xiao, Francis J Hornicek, Zhenfeng Duan
Synovial sarcoma is a highly aggressive but rare form of soft tissue malignancy that primarily affects the extremities of the arms or legs, for which current chemotherapeutic agents have not been proven to be very effective. The cyclin-dependent kinase 4/6-retinoblastoma protein (CDK4/6-Rb) pathway of cell cycle control is known to be aberrant in a large proportion of cancers. Recently, CDK4 inhibitors have successfully been used pre-clinically for the treatment of many human cancers, and in 2015, following the success of clinical trials, the FDA approved the first selective CDK4/6 inhibitor, palbociclib, for the treatment of endocrine therapy resistant breast cancers...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29669860/thermal-proteome-profiling-of-breast-cancer-cells-reveals-proteasomal-activation-by-cdk4-6-inhibitor-palbociclib
#13
Teemu P Miettinen, Julien Peltier, Anetta Härtlova, Marek Gierliński, Valerie M Jansen, Matthias Trost, Mikael Björklund
Palbociclib is a CDK4/6 inhibitor approved for metastatic estrogen receptor-positive breast cancer. In addition to G1 cell cycle arrest, palbociclib treatment results in cell senescence, a phenotype that is not readily explained by CDK4/6 inhibition. In order to identify a molecular mechanism responsible for palbociclib-induced senescence, we performed thermal proteome profiling of MCF7 breast cancer cells. In addition to affecting known CDK4/6 targets, palbociclib induces a thermal stabilization of the 20S proteasome, despite not directly binding to it...
April 18, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29623577/use-of-dual-mtor-inhibitor-mln0128-against-everolimus-resistant-breast-cancer
#14
Karineh Petrossian, Duc Nguyen, Chiao Lo, Noriko Kanaya, George Somlo, Yvonne Xiaoyong Cui, Chiun-Sheng Huang, Shiuan Chen
PURPOSE: HR+/HER2- aromatase inhibitor-resistant metastatic breast cancer can be treated with everolimus and a second AI until the cancer recurs. Targeting these everolimus-resistant patients with the latest standard of care, CDK4/6 inhibitors, has not been clearly addressed. Understanding the signaling transduction pathways, which everolimus resistance activates, will elucidate the mechanisms and offer treatment strategies of everolimus resistance. METHODS: To mimic the clinical setting, letrozole-resistant cells were used to generate an everolimus-resistant model (RAD-R)...
April 5, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29617654/identification-of-cdc25-as-a-common-therapeutic-target-for-triple-negative-breast-cancer
#15
Jeff C Liu, Letizia Granieri, Mariusz Shrestha, Dong-Yu Wang, Ioulia Vorobieva, Elizabeth A Rubie, Rob Jones, YoungJun Ju, Giovanna Pellecchia, Zhe Jiang, Carlo A Palmerini, Yaacov Ben-David, Sean E Egan, James R Woodgett, Gary D Bader, Alessandro Datti, Eldad Zacksenhaus
CDK4/6 inhibitors are effective against cancer cells expressing the tumor suppressor RB1, but not RB1-deficient cells, posing the challenge of how to target RB1 loss. In triple-negative breast cancer (TNBC), RB1 and PTEN are frequently inactivated together with TP53. We performed kinome/phosphatase inhibitor screens on primary mouse Rb/p53-, Pten/p53-, and human RB1/PTEN/TP53-deficient TNBC cell lines and identified CDC25 phosphatase as a common target. Pharmacological or genetic inhibition of CDC25 suppressed growth of RB1-deficient TNBC cells that are resistant to combined CDK4/6 plus CDK2 inhibition...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29582246/current-treatment-patterns-among-postmenopausal-women-with-hr-her2-metastatic-breast-cancer-in-us-community-oncology-practices-an-observational-study
#16
Deborah Goldschmidt, Anand A Dalal, Hela Romdhani, Sneha Kelkar, Annie Guerin, Genevieve Gauthier, Eric Q Wu, Polly Niravath, Tania Small
INTRODUCTION: Recent approval of novel agents has changed the treatment landscape for post menopausal women with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer (mBC). The objective of this study was to describe contemporary treatment patterns among postmenopausal women with HR+/HER2- mBC in the real-world setting. METHODS: Data were collected from 64 community oncologists in the US between February and June 2017 using an online medical records extraction tool...
March 26, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29581135/er-breast-cancers-resistant-to-prolonged-neoadjuvant-letrozole-exhibit-an-e2f4-transcriptional-program-sensitive-to-cdk4-6-inhibitors
#17
Angel Guerrero-Zotano, Thomas Stricker, Luigi Formisano, Katherine E Hutchinson, Daniel G Stover, Kyung-Min Lee, Luis J Schwarz, Jennifer M Giltnane, Monica V Estrada, Valerie M Jansen, Alberto Servetto, Joaquín Gavilá, José Alejandro Pérez-Fidalgo, Ana Lluch, Antonio Llombart-Cussac, Mohamed Amine Bayar, Stefan Michiels, Fabrice Andre, Monica Arnedos, Vicente Guillem, Amparo Ruiz-Simon, Carlos L Arteaga
PURPOSE: This study aimed to identify biomarkers of resistance to endocrine therapy in ER+ breast cancers (BC) treated with prolonged neoadjuvant letrozole. Experimental Design: We performed targeted DNA and RNA-sequencing in 68 ER+ BC from patients treated with preoperative letrozole (median 7 months). Results:Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC>1, FDR<0...
March 26, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29576629/update-breast-cancer-2018-part-1-primary-breast-cancer-and-biomarkers
#18
Florin-Andrei Taran, Andreas Schneeweiss, Michael P Lux, Wolfgang Janni, Andreas D Hartkopf, Naiba Nabieva, Friedrich Overkamp, Hans-Christian Kolberg, Peyman Hadji, Hans Tesch, Achim Wöckel, Johannes Ettl, Diana Lüftner, Markus Wallwiener, Volkmar Müller, Matthias W Beckmann, Erik Belleville, Diethelm Wallwiener, Sara Y Brucker, Peter A Fasching, Tanja N Fehm, Florian Schütz
This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery...
March 2018: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/29564743/a-gene-expression-signature-of-retinoblastoma-loss-of-function-predicts-resistance-to-neoadjuvant-chemotherapy-in-er-positive-her2-positive-breast-cancer-patients
#19
Emanuela Risi, Andrea Grilli, Ilenia Migliaccio, Chiara Biagioni, Amelia McCartney, Cristina Guarducci, Martina Bonechi, Matteo Benelli, Stefania Vitale, Laura Biganzoli, Silvio Bicciato, Angelo Di Leo, Luca Malorni
PURPOSE: HER2-positive (HER2+) breast cancers show heterogeneous response to chemotherapy, with the ER-positive (ER+) subgroup deriving less benefit. Loss of retinoblastoma tumor suppressor gene (RB1) function has been suggested as a cardinal feature of breast cancers that are more sensitive to chemotherapy and conversely resistant to CDK4/6 inhibitors. We performed a retrospective analysis exploring RBsig, a gene signature of RB loss, as a potential predictive marker of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients...
March 22, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29564714/preclinical-and-clinical-development-of-palbociclib-and-future-perspectives
#20
REVIEW
E Martínez de Dueñas, J Gavila-Gregori, S Olmos-Antón, A Santaballa-Bertrán, A Lluch-Hernández, E J Espinal-Domínguez, M Rivero-Silva, A Llombart-Cussac
Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy...
March 21, 2018: Clinical & Translational Oncology
keyword
keyword
110591
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"