keyword
https://read.qxmd.com/read/38390439/cerebral-venous-sinus-thrombosis-in-a-patient-treated-with-ribociclib-for-metastatic-breast-cancer-case-reports-and-literature-review
#21
Baha Sharaf, Zeina Othman, Hala Abu Faris, Malak Al-Bitar, Qasem Al-Zoubi, Dima Abu Laban, Hala Abu-Jaish, Hikmat Abdel-Razeq
Breast cancer is the most diagnosed cancer among women worldwide. Cyclin dependent kinase 4/6 inhibitors (ribociclib, palbociclib, and abemaciclib) modulate endocrine resistance and are widely used treatment for patients with advanced-stage hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Reports of both venous and arterial thromboembolic events, as a complication of cyclin dependent kinase 4/6 inhibitors, are increasingly recognized, but none involved cerebral venous sinus...
2024: SAGE Open Medical Case Reports
https://read.qxmd.com/read/38389643/therapeutic-effects-of-cdk4-6-inhibitors-in-gastric-and-colonic-metastases-from-breast-cancer-a-case-report
#22
Akinori Sasaki, Shuko Masuda, Tsubasa Yoshioka, Akira Saito, Yasuaki Motomura
Breast cancer often metastasizes to the lungs, bones, liver, and brain; however, gastric and colonic metastases from breast cancer are rare. Nevertheless, here, we present the case of a 50-year-old woman diagnosed with recurrent breast cancer, exhibiting gastric and colonic metastases that were detected when she experienced intermittent abdominal pain. The differentiation between primary gastric cancer and metastasis from breast cancer was made through immunohistochemical staining. The patient underwent treatment with palbociclib, a cyclin-dependent kinase (CDK)4/6 inhibitor, and anastrozole, with no significant adverse effects...
January 2024: Curēus
https://read.qxmd.com/read/38387111/identifying-prognostic-biomarkers-for-palbociclib-add-on-therapy-in-fulvestrant-resistant-breast-cancer-using-cell-free-dna-sequencing
#23
JOURNAL ARTICLE
T Takeshita, T Iwamoto, N Niikura, K Watanabe, Y Kikawa, K Kobayashi, N Iwakuma, T Okamura, H Tada, S Ozaki, T Okuno, U Toh, Y Yamamoto, M Tsuneizumi, H Ishiguro, N Masuda, S Saji
BACKGROUND: The FUTURE trial (UMIN000029294) demonstrated the safety and efficacy of adding palbociclib after fulvestrant resistance in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced and metastatic breast cancer (ABC/MBC). In this planned sub-study, cancer panel sequencing of cell-free DNA (cfDNA) was utilized to explore prognostic and predictive biomarkers for further palbociclib treatment following fulvestrant resistance...
February 21, 2024: ESMO Open
https://read.qxmd.com/read/38385117/recommendations-for-cyclin%C3%A2-dependent-kinase-4-6-inhibitor-treatments-in-the-context-of-co%C3%A2-morbidity-and-drug-interactions-review
#24
REVIEW
Mehmet Teomete, Devrim Cabuk, Taner Korkmaz, Selcuk Seber, Ozge Fulya Ozturk, Birkan Aver, Atila Karaalp, Gul Basaran
Breast cancer is most frequently diagnosed among women aged 65-74 years and the prevalence of comorbidities in elderly patients with breast cancer is 32.2%. In addition, polypharmacy is quite common in these patients. Understanding the interaction between breast cancer treatment modalities and comorbidities is important, particularly in elderly patients, as comorbidities affect the choice of appropriate treatment and are independent risk factors for survival. A total of three oral cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), palbociclib, ribociclib and abemaciclib, notably prolonged progression-free survival when combined with endocrine therapy (ET), compared with ET alone in patients with advanced breast cancer (ABC)...
April 2024: Oncology Letters
https://read.qxmd.com/read/38354504/dispersive-liquid-liquid-microextraction-followed-by-sweeping-micellar-electrokinetic-chromatography-tandem-mass-spectrometry-for-determination-of-six-breast-cancer-drugs-in-human-plasma
#25
JOURNAL ARTICLE
Zvonimir Mlinarić, Lu Turković, Miranda Sertić
Herein, we have developed a novel method of aqueous-sample dispersive liquid-liquid microextraction (AqS-DLLME) followed by sweeping micellar electrokinetic chromatography-tandem mass spectrometry (MEKC-MS/MS) for simultaneous determination of breast cancer drugs letrozole, anastrozole, palbociclib, ribociclib, abemaciclib, and fulvestrant in human plasma. Coupling of MEKC to MS was possible due to the use of ammonium perfluorooctanoate (APFO) as a volatile surfactant. The MEKC and MS conditions were optimized to achieve a fast, sensitive, selective, and green analysis enabling full separation of the analytes within 16 min...
February 3, 2024: Journal of Chromatography. A
https://read.qxmd.com/read/38344632/role-of-cyclin-dependent-kinase-4-6-in-metastatic-breast-cancer-real-world-data-from-a-tertiary-care-institute-in-eastern-india
#26
JOURNAL ARTICLE
Saroj Kumar Das Majumdar, Sandip Kumar Barik, Ashutosh Pattanaik, Deepak Kumar Das, Dillip Kumar Parida
Introduction CDK4/6 inhibitors currently approved for patients with hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer include palbociclib, ribociclib, and abemaciclib. This study aims to report on the treatment outcomes and real-world data regarding the use of CDK4/6 inhibitors in the treatment of ER+/HER2- metastatic breast cancer at a tertiary care institute in Eastern India. Materials and methods The present study is a retrospective analysis of data from patients with metastatic HR+/HER2- breast cancer who were treated with CDK4/6 inhibitors at a tertiary care institute in Eastern India between 2015 and 2022...
January 2024: Curēus
https://read.qxmd.com/read/38344066/mir-6883-downregulates-hif1%C3%AE-in-colorectal-and-breast-cancer-cells
#27
JOURNAL ARTICLE
Nicole A Jensen-Velez, Lindsey Carlsen, Wafik S El-Deiry
Colorectal cancer (CRC) and breast cancer (BC) are deadly diseases that rank as the second and fourth leading causes of cancer-related deaths, respectively. We have previously shown that miR-6883 targets CDK4/6 and that palbociclib-mediated CDK4/6 inhibition destabilizes HIF1α. We hypothesize that miR-6883 downregulates HIF1α in CRC and BC cells. miR-6883 was transfected into cells under normoxia or hypoxia and western blot analysis revealed that miR-6883 downregulates CDK4/6 and HIF1α in CRC and BC cells, pointing to miR-6883 as a promising therapeutic to target hypoxic tumors or HIF1α-deregulated cancer cells...
2024: microPublication. Biology
https://read.qxmd.com/read/38342885/palbociclib-safe-and-effective-in-an-85-year-old-female-with-metastatic-bilateral-breast-cancer
#28
JOURNAL ARTICLE
Asif Husain Osmani
Null.
February 2024: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://read.qxmd.com/read/38340010/proton-pump-inhibitors-and-cyclin-dependent-kinase-4-6-inhibitors-in-patients-with-breast-cancer
#29
JOURNAL ARTICLE
Kaori Takahashi, Ryuji Uozumi, Toru Mukohara, Tetsu Hayashida, Midori Iwabe, Hirotoshi Iihara, Kanako Kusuhara-Mamishin, Yuko Kitagawa, Masami Tsuchiya, Mika Kitahora, Aiko Nagayama, Shinkichi Kosaka, Yoshimi Asano-Niwa, Tomoko Seki, Koji Ohnuki, Akio Suzuki, Fumiko Ono, Manabu Futamura, Hitoshi Kawazoe, Tomonori Nakamura
BACKGROUND: Proton pump inhibitors (PPIs) reduce the bioavailability of several anticancer drugs. The impact of PPIs co-administered with cyclin-dependent kinase 4 and 6 inhibitors is controversial. We aimed to clarify whether the concomitant use of PPIs impacts palbociclib and abemaciclib effectiveness in breast cancer treatment. PATIENTS AND METHODS: This multicenter, retrospective, observational study, conducted across 4 medical institutions in Japan, consecutively included patients with endocrine-resistant metastatic breast cancer, receiving palbociclib or abemaciclib between December 2017 and August 2022...
February 10, 2024: Oncologist
https://read.qxmd.com/read/38338777/identification-of-a-panel-of-mirnas-associated-with-resistance-to-palbociclib-and-endocrine-therapy
#30
JOURNAL ARTICLE
Rosalba Torrisi, Valentina Vaira, Laura Giordano, Bethania Fernandes, Giuseppe Saltalamacchia, Raffaella Palumbo, Carlo Carnaghi, Vera Basilico, Francesco Gentile, Giovanna Masci, Rita De Sanctis, Armando Santoro
We investigated whether we could identify a panel of miRNAs associated with response to treatment in tumor tissues of patients with Hormone Receptor-positive/HER2-negative metastatic breast cancer treated with endocrine therapy (ET) and the CDK4/6 inhibitor (CDK4/6i)i palbociclib. In total, 52 patients were evaluated, with 41 receiving treatment as the first line. The overall median PFS was 20.8 months (range 2.5-66.6). In total, 23% of patients experienced early progression (<6 months). Seven miRNAs ( miR-378e , miR-1233 , miR-99b-5p , miR-1260b , miR-448 , -miR-1252-5p , miR-324-3p , miR-1233-3p ) showed a statistically significant negative association with PFS...
January 25, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38332945/efficacy-and-activity-of-treatments-after-progression-from-palbociclib-plus-endocrine-therapy-in-patients-with-hr-her2-metastatic-breast-cancer-a-prospective-monocentric-study
#31
JOURNAL ARTICLE
Raffaella Palumbo, Erica Quaquarini, Giuseppe Saltalamacchia, Alberto Malovini, Pietro Lapidari, Barbara Tagliaferri, Ludovica Mollica, Cristina Maria Teragni, Chiara Barletta, Laura Deborah Locati, Federico Sottotetti
BACKGROUND: Breast cancer is the most frequent tumour worldwide, and the HR+ /HER2- subtype is the most common. For this tumour type, endocrine therapy (ET) is the mainstay of treatment. The association of ET and CDK4/6 inhibitors (CDK4/6i) represents the gold standard for first-line or second-line therapies. However, the optimal therapeutic strategy after CDK4/6i progression is still a matter of debate, with several randomized clinical trials still ongoing. PATIENTS AND METHODS: This is an observational, prospective, real-world study including women with HR+ /HER2- metastatic breast cancer progressing to palbociclib plus ET...
2024: Drugs in Context
https://read.qxmd.com/read/38326452/comparative-overall-survival-of-cdk4-6-inhibitors-in-combination-with-endocrine-therapy-in-advanced-breast-cancer
#32
JOURNAL ARTICLE
Coralea Kappel, Mitchell J Elliott, Vikaash Kumar, Michelle B Nadler, Alexandra Desnoyers, Eitan Amir
Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall survival (OS). A robust comparative evaluation of OS, safety, and tolerability of the three drugs is warranted. A systematic literature search identified phase 3 randomized clinical trials reporting OS of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy in ER-positive/HER2-negative advanced breast cancer. Trial-level data on OS and common and serious adverse events (AE) were extracted for each drug...
February 7, 2024: Scientific Reports
https://read.qxmd.com/read/38324568/cell-cycle-plasticity-underlies-fractional-resistance-to-palbociclib-in-er-her2-breast-tumor-cells
#33
JOURNAL ARTICLE
Tarek M Zikry, Samuel C Wolff, Jolene S Ranek, Harris M Davis, Ander Naugle, Namit Luthra, Austin A Whitman, Katarzyna M Kedziora, Wayne Stallaert, Michael R Kosorok, Philip M Spanheimer, Jeremy E Purvis
The CDK4/6 inhibitor palbociclib blocks cell cycle progression in Estrogen receptor-positive, human epidermal growth factor 2 receptor-negative (ER+/HER2-) breast tumor cells. Despite the drug's success in improving patient outcomes, a small percentage of tumor cells continues to divide in the presence of palbociclib-a phenomenon we refer to as fractional resistance. It is critical to understand the cellular mechanisms underlying fractional resistance because the precise percentage of resistant cells in patient tissue is a strong predictor of clinical outcomes...
February 13, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38320891/cyclin-dependent-kinase-4-6-inhibitors-as-neoadjuvant-therapy-of-hormone-receptor-positive-her2-negative-early-breast-cancer-what-do-we-know-so-far
#34
REVIEW
Ioanna Ploumaki, Efthymios Triantafyllou, Ioannis-Alexios Koumprentziotis, Konstantinos Karampinos, Konstantinos Drougkas, Ioannis Karavolias, Elias Kotteas
The introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors to the treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer is regarded as one of the greatest achievements of the last decades in breast oncology. To date, palbociclib, abemaciclib and ribociclib are the 3 approved CDK4/6 inhibitors that combined with endocrine therapy are now considered as the standard first-line treatment of metastatic HR+/HER2- breast cancer. The great success of these drugs in the setting of metastatic disease and the need to combat the high risk of recurrence have paved the way for a number of clinical trials to explore the use of CDK4/6 inhibitors in the neoadjuvant treatment of early breast cancer...
January 16, 2024: Clinical Breast Cancer
https://read.qxmd.com/read/38310597/the-efficacy-of-palbociclib-and-ribociclib-in-the-first-line-treatment-of-metastatic-hormone-receptor-positive-human-epidermal-growth-factor-receptor-2-negative-breast-cancer-in-male-patients-a-turkish-oncology-group-tog-study
#35
JOURNAL ARTICLE
Hasan Çağrı Yıldırım, Yasin Kutlu, Emel Mutlu, Musa Barış Aykan, Mustafa Korkmaz, Selim Yalçın, Teoman Şakalar, Özde Melisa Celayir, Erkan Kayıkçıoğlu, Ferit Aslan, Emre Hafızoğlu, Yunus Emre Altıntaş, Merve Keskinkılıç, Elvin Chalabiyev, Abdussamet Çelebi, Bengü Dursun, Caner Kapar, Miraç Özen, Ömer Acar, Özgecan Dülgar, Engin Kut, Sedat Biter, Fatih Kus, Elvina Almuradova, Atike Pınar Erdoğan, Seray Saray, Deniz Can Güven, Eda Tanrıkulu Şimşek, Necdet Üskent, Yasemin Kemal, Burcu Çakar, Özgür Açıkgöz, Saadettin Kılıçkap, Sercan Aksoy
INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer...
February 4, 2024: International Journal of Clinical Oncology
https://read.qxmd.com/read/38302240/flow-cytometry-assisted-quantification-of-cell-cycle-arrest-in-cancer-cells-treated-with-cdk4-6-inhibitors
#36
JOURNAL ARTICLE
Vanessa Klapp, Norma Bloy, Carlos Jiménez-Cortegana, Aitziber Buqué, Giulia Petroni
Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (i.e., palbociclib, abemaciclib, and ribociclib) are well known for their capacity to mediate cytostatic effects by promoting cell cycle arrest in the G1 phase, thus inhibiting cancer cell proliferation. Cytostatic effects induced by CDK4/6 inhibitors can be transient or lead to a permanent state of cell cycle arrest, commonly defined as cellular senescence. Induction of senescence is often associated to metabolic modifications and to the acquisition of a senescence-associated secretory phenotype (SASP) by cancer cells, which in turn can promote or limit antitumor immunity (and thus the efficacy of CDK4/6 inhibitors) depending on SASP components...
2024: Methods in Cell Biology
https://read.qxmd.com/read/38288438/the-adverse-events-of-cdk4-6-inhibitors-for-hr-her2-breast-cancer-an-umbrella-review-of-meta-analyses-of-randomized-controlled-trials
#37
Dongqing Pu, Yue Wu, Debo Xu, Guangxi Shi, Hanhan Chen, Dandan Feng, Mengdi Zhang, Jingwei Li
Background: The clinical selection of three CDK4/6 inhibitors presents a challenging issue, owing to the absence of distinct clinical case characteristics, biomarkers, and their comparable clinical benefits in progression-free survival and overall survival To inform clinical treatment decisions, we conducted a comprehensive evaluation of the adverse events associated with CDK4/6 inhibitors in combination with endocrine therapy for hazard ratio+/HER2-breast cancer. Methods: We searched Cochrane, PubMed, Embase, and Web of Science databases from their inception until 1 August 2022...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38283222/novel-indolyl-1-2-4-triazole-derivatives-as-potential-anti-proliferative-agents-in-silico-studies-synthesis-and-biological-evaluation
#38
JOURNAL ARTICLE
Sarah A Ghobish, Khaled O Mohamed, Nahla Farag, Doaa B Farag
A new series of indolyl 1,2,4-triazole scaffolds was designed, synthesised, and biologically evaluated for their inhibitory activity against both CDK4 and CDK6. The results ranged from 0.049 μM to 3.031 μM on CDK4 and from 0.075 μM to 1.11 μM on CDK6 when compared to staurosporine, with IC50 values of 1.027 and 0.402 μM, respectively. Moreover, all compounds were tested for their cytotoxicity against two breast cancer cell lines, MCF-7 and MDA-MB-231. All of the synthesised compounds showed promising anti-proliferative activity, with two compounds Vf (IC50 = 2...
January 25, 2024: RSC medicinal chemistry
https://read.qxmd.com/read/38277141/co-targeting-cdk4-6-and-brd4-promotes-senescence-and-ferroptosis-sensitivity-in-cancer
#39
JOURNAL ARTICLE
Xianbing Zhu, Zheng Fu, Kendall Dutchak, Azadeh Arabzadeh, Simon Milette, Jutta Steinberger, Geneviève Morin, Anie Monast, Virginie Pilon, Tim Kong, Bianca N Adams, Erika Prando Munhoz, Hannah Jb Hosein, Tianxu Fang, Jing Su, Yibo Xue, Roni Rayes, Veena Sangwan, Logan A Walsh, Guojun Chen, Daniela F Quail, Jonathan D Spicer, Morag Park, David Dankort, Sidong Huang
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for breast cancer treatment and show activity against other malignancies, including KRAS-mutant non-small cell lung cancer (NSCLC). However, the clinical efficacy of CDK4/6 inhibitors is limited due to frequent drug resistance and their largely cytostatic effects. Through a genome-wide cDNA screen, we identified that bromodomain-containing protein 4 (BRD4) overexpression conferred resistance to the CDK4/6 inhibitor palbociclib in KRAS-mutant NSCLC cells...
January 26, 2024: Cancer Research
https://read.qxmd.com/read/38252901/overall-survival-with-palbociclib-plus-letrozole-in-advanced-breast-cancer
#40
RANDOMIZED CONTROLLED TRIAL
Dennis J Slamon, Véronique Diéras, Hope S Rugo, Nadia Harbeck, Seock-Ah Im, Karen A Gelmon, Oleg N Lipatov, Janice M Walshe, Miguel Martin, Mariana Chavez-MacGregor, Eustratios Bananis, Eric Gauthier, Dongrui R Lu, Sindy Kim, Richard S Finn
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PALOMA-2 demonstrated statistically and clinically significant improvement in progression-free survival with palbociclib plus letrozole versus placebo plus letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (ABC)...
March 20, 2024: Journal of Clinical Oncology
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