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https://www.readbyqxmd.com/read/29904310/dramatic-response-to-cyclin-d-dependent-kinase-4-6-inhibitor-in-refractory-poorly-differentiated-neuroendocrine-carcinoma-of-the-breast
#1
Allison Shanks, Julia Choi, Vinit Karur
Neuroendocrine tumors are a rare subset of breast carcinomas. Commonly, platinum-based doublet is used as a systemic treatment option for high-grade neuroendocrine carcinomas from lung, gastrointestinal, and genitourinary origins. In comparison to other breast cancers, neuroendocrine carcinomas have unique genomic features and different treatment strategies. We present a patient with high-grade neuroendocrine carcinoma of the breast who had a successful and durable response to the cyclin D-dependent kinase (CDK) 4/6 inhibitor palbociclib in conjunction with endocrine therapy...
July 2018: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/29864945/octyl-gallate-and-gallic-acid-isolated-from-terminalia-bellarica-regulates-normal-cell-cycle-in-human-breast-cancer-cell-lines
#2
Mary Selesty Sales, Anita Roy, Ludas Antony, Sakhila K Banu, Selvaraj Jeyaraman, Rajalakshmi Manikkam
Herbal medicines stand unique and effective in treating human diseases. Terminalia bellarica (T. bellarica) is a potent medicinal herb, with a wide range of pharmacological activities. The present study was aimed to evaluate the effect of octyl gallate (OG) and gallic acid (GA) isolated from methanolic fruit extract of T. bellirica to inhibit the survival of breast cancer cells (MCF-7 & MDA-MB-231). Both OG & GA exhibited decreased MCF-7 & MDA-MB-231 survival and induced apoptosis, with IC50 value of OG and GA as 40 μM and 80 μM respectively...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29804650/cdk4-6-inhibitors-in-combination-with-hormone-therapy-for-hr-her2-advanced-breast-cancer-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#3
Yunfu Deng, Guangzhi Ma, Wen Li, Ting Wang, Yaqin Zhao, Qiang Wu
BACKGROUND: This meta-analysis of randomized controlled trials aimed to comprehensively assess the efficacy and toxicity of cyclin-dependent kinase (CDK) 4/6 inhibitors in advanced breast cancer (ABC) with hormone-receptor positive (HR+ ) and human epidermal growth factor receptor 2 negative (HER2- ) disease. METHODS: We performed a systematical search using Cochrane Library, PubMed, Embase, and Web of Science up to March 2018. Only phase 2 and 3 randomized clinical trials assessing the efficacy and toxicity of the combination regimen of CDK4/6 inhibitors plus hormone therapy compared with hormone therapy alone were eligible for this meta-analysis...
May 4, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29799329/cost-effectiveness-of-ribociclib-plus-letrozole-versus-palbociclib-plus-letrozole-and-letrozole-monotherapy-in-the-first-line-treatment-of-postmenopausal-women-with-hr-her2-advanced-or-metastatic-breast-cancer-a-u-s-payer-perspective
#4
Rohit Mistry, Jessica R May, Gaurav Suri, Kate Young, Diana Brixner, Gary Oderda, Joseph Biskupiak, Derek Tang, Subrata Bhattacharyya, Dinesh Mishra, Devarshi Bhattacharyya, Anand A Dalal
BACKGROUND: U.S. regulatory approvals of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors ribociclib and palbociclib as add-ons to letrozole greatly enhance the prospects for treating postmenopausal women with hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer. Clinical trials have established that the combination of a CDK 4/6 inhibitor with letrozole can significantly improve progression-free survival (PFS) versus letrozole monotherapy and is safe and well tolerated...
June 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29789630/preclinical-evaluation-of-ribociclib-and-its-synergistic-effect-in-combination-with-alpelisib-in-non-keratinizing-nasopharyngeal-carcinoma
#5
Chi-Hang Wong, Brigette B Y Ma, Connie W C Hui, Kwok-Wai Lo, Edwin P Hui, Anthony T C Chan
Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that induces G1 arrest by blocking the formation of cyclin D1-Cdk4/6 complex and inhibiting retinoblastoma (RB) phosphorylation. Cyclin D1 is overexpressed in over 90% of nasopharyngeal carcinoma (NPC) and CCND1 gene activation plays a critical role in NPC pathogenesis. This study evaluated the preclinical activities of ribociclib in NPC cell lines and patient derived xenograft (PDX) models. Over 95% cell growth inhibition was observed at 96 hours after ribociclib treatment...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29751334/treatment-of-advanced-her2-positive-breast-cancer-2018-and-beyond
#6
REVIEW
Noam Pondé, Mariana Brandão, Georges El-Hachem, Emilie Werbrouck, Martine Piccart
In the 1980s the importance of HER2 signalling to the aberrant behaviour of a subset of breast cancer cells was recognized for the first time and, consequently, a hitherto unknown subtype of breast cancer - HER2-positive (HER2+) breast cancer was identified. The development of the anti-HER2 class of drugs, first with trastuzumab, followed closely by lapatinib, pertuzumab, and T-DM1, has improved outcomes dramatically. Nevertheless, metastatic HER2+ breast cancer remains an incurable disease and new therapeutic options are needed...
June 2018: Cancer Treatment Reviews
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
#7
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/29721855/id1-and-sonic-hedgehog-mediate-cell-cycle-reentry-and-apoptosis-induced-by-amyloid-beta-peptide-in-post-mitotic-cortical-neurons
#8
A-Ching Chao, Chien-Hui Chen, Shih-Hsin Chang, Chao-Tzu Huang, Wei-Chao Hwang, Ding-I Yang
Amyloid beta-peptide (Aβ), the neurotoxic component of senile plaques in Alzheimer's disease (AD) brains, is known to trigger cell cycle reentry in post-mitotic neurons followed by apoptosis. However, the underlying mechanisms remain unclear. Recently, we have reported that Aβs stimulate the expression of inhibitor of differentiation-1 (Id1) to induce sonic hedgehog (SHH) (Hung et al., Mol Neurobiol 53(2):793-809, 2016), and both are mitogens capable of triggering cell cycle progression. In this work, we tested the hypothesis that Aβ-induced Id1 and SHH contribute to cell cycle reentry leading to apoptosis in neurons...
May 2, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29720233/real-world-evidence-analysis-of-palbociclib-prescribing-patterns-for-patients-with-advanced-metastatic-breast-cancer-treated-in-community-oncology-practice-in-the-usa-one-year-post-approval
#9
J K Kish, M A Ward, D Garofalo, H V Ahmed, L McRoy, J Laney, G Zanotti, J Braverman, H Yu, B A Feinberg
BACKGROUND: Rapidly evolving understanding of cancer biology has presented novel opportunities to translate that understanding into clinically relevant therapy. Palbociclib, a novel, first-in-class cyclin-dependent kinase (CDK) 4/6 inhibitor was approved in the USA in February 2015 for the treatment of advanced/metastatic breast cancer. We examined real-world evidence in the first year post approval to understand the clinical and demographic characteristics of patients treated with palbociclib in community oncology practices and the dosing, treatment, and complete blood count (CBC) monitoring patterns...
May 2, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29700711/cyclin-dependent-kinase-4-6-inhibitors-in-hormone-receptor-positive-early-breast-cancer-preliminary-results-and-ongoing-studies
#10
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/29687202/attenuation-of-aluminum-chloride-induced-neuroinflammation-and-caspase-activation-through-the-akt-gsk-3%C3%AE-pathway-by-hesperidin-in-wistar-rats
#11
Arokiasamy Justin-Thenmozhi, Mathiyazahan Dhivya Bharathi, Ramaraj Kiruthika, Thamilarasan Manivasagam, Anupom Borah, Musthafa Mohamed Essa
Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. Previous reports from our laboratory indicated the neuroprotective effect of hesperidin against aluminum chloride (AlCl3 )-induced memory loss, acetylcholine esterase hyperactivity, oxidative stress, and enhanced expression of amyloid β protein biosynthesis-related markers. However, their role on AlCl3 -induced inflammation, caspase activation, Tau pathology, altered Akt/GSK 3β signaling pathway, and Aβ clearance marker has not yet been fully elucidated...
April 23, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29685881/cycling-toward-progress-ribociclib-a-cdk-4-6-inhibitor-for-breast-cancer
#12
Laura Spring, Aditya Bardia
Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor-positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer. Clin Cancer Res; 24(13); 1-3. ©2018 AACR. See related article by Shah et al., p. 2999 .
April 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29673999/ribociclib-shows-potential-for-pharmacokinetic-drug-drug-interactions-being-a-substrate-of-abcb1-and-potent-inhibitor-of-abcb1-abcg2-and-cyp450-isoforms-in-vitro
#13
Ales Sorf, Jakub Hofman, Radim Kučera, Frantisek Staud, Martina Ceckova
Ribociclib is a novel cyclin-dependent kinase (CDK) 4 and 6 selective inhibitor that recently gained breakthrough therapy status and global approval for advanced breast cancer treatment. ATP-binding cassette (ABC) transporters may become a site of severe drug interactions and a mechanism of multidrug resistance (MDR) development. With respect to rapid progress of ribociclib in the clinical field, we aimed to identify its interactions with ABC transporters and cytochrome P450 (CYP) isoenzymes and evaluate its potential to overcome transporter-mediated MDR using established in vitro methods...
April 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29666673/pan-cdk-inhibition-augments-cisplatin-lethality-in-nasopharyngeal-carcinoma-cell-lines-and-xenograft-models
#14
Nicholas L Syn, Pei Li Lim, Li Ren Kong, Lingzhi Wang, Andrea Li-Ann Wong, Chwee Ming Lim, Thomas Kwok Seng Loh, Gerhard Siemeister, Boon Cher Goh, Wen-Son Hsieh
In addition to their canonical roles in regulating cell cycle transition and transcription, cyclin-dependent kinases (CDKs) have been shown to coordinate DNA damage response pathways, suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human malignancies. Here, we report that roniciclib (BAY1000394), a potent pan-CDK inhibitor, displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma (NPC) models...
2018: Signal Transduction and Targeted Therapy
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
#15
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/29486476/voruciclib-a-potent-cdk4-6-inhibitor-antagonizes-abcb1-and-abcg2-mediated-multi-drug-resistance-in-cancer-cells
#16
Pranav Gupta, Yun-Kai Zhang, Xiao-Yu Zhang, Yi-Jun Wang, Kimberly W Lu, Timothy Hall, Richard Peng, Dong-Hua Yang, Ni Xie, Zhe-Sheng Chen
BACKGROUND/AIMS: The overexpression of ATP-Binding Cassette (ABC) transporters has known to be one of the major obstacles impeding the success of chemotherapy in drug resistant cancers. In this study, we evaluated voruciclib, a CDK 4/6 inhibitor, for its chemo-sensitizing activity in ABCB1- and ABCG2- overexpressing cells. METHODS: Cytotoxicity and reversal effect of voruciclib was determined by MTT assay. The intracellular accumulation and efflux of ABCB1 and ABCG2 substrates were measured by scintillation counter...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29470723/cyclin-dependent-kinase-4-6-inhibitors-as-first-line-treatment-for-post-menopausal-metastatic-hormone-receptor-positive-breast-cancer-patients-a-systematic-review-and-meta-analysis-of-phase-iii-randomized-clinical-trials
#17
Allan Ramos-Esquivel, Hellen Hernández-Steller, Marie-France Savard, Denis Ulises Landaverde
BACKGROUND: To compare the efficacy and toxicity of the combination of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors and nonsteroidal aromatase inhibitors (AI) versus AI alone as first-line therapy for patients with advanced hormone receptor-positive breast cancer. MATERIALS AND METHODS: Phase III randomized clinical trials (RCT) were identified after a systematic review of electronic databases. A random-effect model was used to determine the pooled hazard ratio (HR) for progression-free survival (PFS) using the inverse-variance method...
February 22, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29464035/upregulation-of-cell-cycle-genes-in-head-and-neck-cancer-patients-may-be-antagonized-by-erufosine-s-down-regulation-of-cell-cycle-processes-in-oscc-cells
#18
Shariq S Ansari, Ashwini K Sharma, Michael Zepp, Elizabet Ivanova, Frank Bergmann, Rainer König, Martin R Berger
The TCGA database was analyzed to identify deregulation of cell cycle genes across 24 cancer types and ensuing effects on patient survival. Pan-cancer analysis showed that head and neck squamous cell carcinoma (HNSCC) ranks amongst the top four cancers showing deregulated cell cycle genes. Also, the median gene expression of all CDKs and cyclins in HNSCC patient samples was higher than that of the global gene expression. This was verified by IHC staining of CCND1 from HNSCC patients. When evaluating the quartiles with highest and lowest expression, increased CCND1/CDK6 levels had negative implication on patient survival...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29445290/molecular-features-of-giant-cell-carcinoma-of-the-lung-a-case-report-and-literature-review
#19
Xin Li, Zihe Zhang, Jinghao Liu, Dan Wang, Sen Wei, Jun Chen
Giant-cell carcinoma of the lung (GCCL) is a rare histological form of poorly differentiated non-small-cell lung cancer, which is classified as a subtype of pulmonary sarcomatoid carcinomas. In this case report, we describe the case of a 50-year-old Chinese male who presented with a pulmonary nodule in the right upper lobe of his lung. After thoracoscopic lobectomy, a histopathologic diagnosis of GCCL was made. He did well postoperatively, showing no local recurrence or distal disease in a 7-year follow-up period...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29436583/antiproliferative-effects-of-the-cdk6-inhibitor-pd0332991-and-its-effect-on-signaling-networks-in-gastric-cancer-cells
#20
Daguang Wang, Yabin Sun, Wei Li, Fei Ye, Yang Zhang, Yuchen Guo, David Y Zhang, Jian Suo
PD0332991 (palbociclib/Ibrance®) is a cyclin-dependent kinase (CDK)4/6 inhibitor that has recently been approved for the treatment of estrogen receptor‑positive advanced breast cancer. The present study investigated the antiproliferative effects of PD0332991 on gastric cancer (GC) cells and the underlying molecular mechanisms. The activity of PD0332991 was tested in several GC cell lines, including AGS, KATO‑Ⅲ, NCI‑N87 and HS746T. Growth inhibitory activity of PD0332991, alone or in combination with fluorouracil (5‑FU), was measured by MTT assay...
May 2018: International Journal of Molecular Medicine
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