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JOURNAL ARTICLE
Makiko Go, Yoshihiro Noguchi, Rikuto Masuda, Hiroki Asano, Michio Kimura, Eiseki Usami, Tomoaki Yoshimura
The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity...
April 15, 2024: International Journal of Cancer. Journal International du Cancer
#2
JOURNAL ARTICLE
Ziyan Yang, Guiyuan Chen
OBJECTIVE: This study aimed to investigate methodologies for the extraction and purification of polysaccharides from Rosa roxburghii Tratt fruits and their impact on various cellular processes in prostate cancer DU145 cells, including survival rate, migration, invasion, cell cycle, and apoptosis. RESULTS: Compared to the control group, the polysaccharide exhibited a significant reduction in the viability, migration, and invasion rates of DU145 cells in a time- and dose-dependent manner within the polysaccharide-treated groups...
April 1, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
#3
JOURNAL ARTICLE
Paula Sobrini-Morillo, Christine Ravot, Chloé Herlédan, Carmen Sánchez-Castellano, Alfonso J Cruz-Jentoft, Claire Falandry
This study describes characteristics, toxicity and survival in old patients with HR+/HER2-breast cancer (BC) treated with CDK4/6 inhibitors. Retrospective observational study that included patients ≥ 75 years with HR+/HER2-BC treated with CDK4/6 inhibitors between 2017 and 2021. Patients' general and cancer-related data were collected. Comprehensive Geriatric Assessment scales were gathered. Adverse events reported before each cycle were included. At the end of the follow-up period, mortality was retrospectively registered from medical records...
February 22, 2024: Seminars in Oncology
#4
Guilherme Vilhais, Diogo Alpuim Costa, Mário Fontes-Sousa, Pedro Casal Ribeiro, Filipa Martinho, Carolina Botelho de Sousa, Catarina Rodrigues Santos, Ida Negreiros, Ana Canastra, Paula Borralho, Ana Guia Pereira, Cristina Marçal, José Germano Sousa, Renata Chaleira, Júlio César Rocha, Conceição Calhau, Ana Faria
Locally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2-negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology...
2024: Frontiers in Oncology
#5
REVIEW
Abha Kulkarni, Jasmeet Singh
INTRODUCTION: Cyclin-dependent kinase (CDK) 4/6 inhibitors are cornerstones in the treatment of Hormone Receptor (HR) positive and Human Epidermal Growth factor (HER2) negative metastatic breast cancer. Given their widespread use in the metastatic setting and emerging use in the adjuvant setting, studying the drug-drug interactions (DDI) of these medications is of utmost importance. AREAS COVERED: This review provides key background information on the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib...
April 11, 2024: Expert Opinion on Drug Metabolism & Toxicology
#6
REVIEW
Kleoniki Apostolidou, Eleni Zografos, Maria Alkistis Papatheodoridi, Oraianthi Fiste, Meletios Athanasios Dimopoulos, Flora Zagouri
Over the past few decades, first-line therapy for treating advanced and metastatic HR+/HER2-breast cancer has transformed due to the introduction of adjuvant endocrine therapy with cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). However, there is an unmet need for novel classes of endocrine therapy with superior efficacy to improve treatment outcomes and overcome CDK4/6i resistance. New generation selective estrogen receptor degraders (SERDs), orally administered and with higher bioavailability, could potentially be the novel compounds to meet this emerging need...
April 4, 2024: Breast: Official Journal of the European Society of Mastology
#7
REVIEW
Alexa J Luboff, David L DeRemer
OBJECTIVE: To review the pharmacology, efficacy, and safety of capivasertib for the treatment of adults with hormone receptor-positive, HER2-negative (HR+/HER2-) locally advanced or metastatic breast cancer with 1 or more PIK3CA/AKT1/PTEN alterations. DATA SOURCES: A literature search was conducted using PubMed and MEDLINE databases, published abstracts, and studies from ClinicalTrials.gov between 2003 and February 2024. Keywords included capivasertib, AZD5363, PI3K/AKT/mTOR pathway, and breast cancer...
April 2, 2024: Annals of Pharmacotherapy
#8
JOURNAL ARTICLE
Fanye Meng, Jinxin Liu, Zhongying Cao, Jiaojiao Yu, Barbara Steurer, Yilin Yang, Yazhou Wang, Xin Cai, Man Zhang, Feng Ren, Alex Aliper, Xiao Ding, Alex Zhavoronkov
Cyclin-dependent kinases (CDKs) are critical cell cycle regulators that are often overexpressed in tumors, making them promising targets for anti-cancer therapies. Despite substantial advancements in optimizing the selectivity and drug-like properties of CDK inhibitors, safety of multi-target inhibitors remains a significant challenge. Macrocyclization is a promising drug discovery strategy to improve the pharmacological properties of existing compounds. Here we report the development of a macrocyclization platform that enabled the highly efficient discovery of a novel, macrocyclic CDK2/4/6 inhibitor from an acyclic precursor (NUV422)...
March 15, 2024: Bioorganic Chemistry
#9
JOURNAL ARTICLE
Takuya Yoshimura, Yuka Hirano, Taiji Hamada, Seiya Yokoyama, Hajime Suzuki, Hirotaka Takayama, Hirono Migita, Takayuki Ishida, Yasunori Nakamura, Masahiro Ohsawa, Akihiro Asakawa, Kiyohide Ishihata, Akihide Tanimoto
Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study...
March 18, 2024: Cancers
#10
JOURNAL ARTICLE
Murad Guliyev, Gülin Alkan Şen, İlkay Gültürk, Nargiz Majidova, Goncagül Akdağ, Ali Ahadzade, Hande Turna, Nebi Serkan Demirci
PURPOSE: Endocrine therapy (ET) in combination with CDK 4/6 inhibitors (CDK 4/6i) is the standard treatment modality for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (mBC). There is uncertainty about the prognostic and predictive value of HER2-low status and whether HER2-low BC is an individual biologic subtype. In this study, we aimed to investigate the prognostic effect of HER2 expression status on survival in mBC patients treated with first-line ET plus CDK 4/6i...
March 25, 2024: Breast Cancer Research and Treatment
#11
JOURNAL ARTICLE
Helena Pla, Eudald Felip, Verónica Obadia, Sonia Pernas, Gemma Viñas, Mireia Margelí, Roser Fort-Culillas, Sonia Del Barco, Nuria Sabaté, Eduard Fort, Clara Lezcano, Beatriz Cirauqui, Vanesa Quiroga, Agostina Stradella, Miguel Gil Gil, Anna Esteve, Sabela Recalde
INTRODUCTION: Cyclin-dependent kinases 4/6 inhibitors (CDK 4/6i) combined with endocrine therapy have become the gold standard in hormone receptor-positive (HR +) HER2-negative (HER2-) metastatic breast cancer (MBC). However, there is a significant lack of data regarding the efficacy and safety of these treatments in elderly patients. We present the results of a real-world data (RWD) cohort stratified by age at treatment initiation (≥ 70 years compared to patients < 70 years)...
March 22, 2024: Clinical & Translational Oncology
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JOURNAL ARTICLE
Erica L Mayer, Yue Ren, Nikhil Wagle, Reshma Mahtani, Cynthia Ma, Angela DeMichele, Massimo Cristofanilli, Jane Meisel, Kathy D Miller, Yara Abdou, Elizabeth C Riley, Rubina Qamar, Priyanka Sharma, Sonya Reid, Natalie Sinclair, Meredith Faggen, Caroline C Block, Naomi Ko, Ann H Partridge, Wendy Y Chen, Michelle DeMeo, Victoria Attaya, Amanda Okpoebo, Jillian Alberti, Yuan Liu, Eric Gauthier, Harold J Burstein, Meredith M Regan, Sara M Tolaney
PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting. METHODS: The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy...
March 21, 2024: Journal of Clinical Oncology
#13
JOURNAL ARTICLE
O Fiste, C Trika, N K Syrigos, E A Kotteas
BACKGROUND: The recent advent of the cyclin-dependent kinase (CDK) 4/6 inhibitors has considerably evolved hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer treatment. Palbociclib, an orally administered pyridopyrimidine derivative, was the first CDK4/6 inhibitor to be introduced into daily clinical practice in combination with classic endocrine backbone, based on progression-free survival (PFS) benefit assessed in the pivotal PALOMA series of randomized clinical trials...
March 2024: European Review for Medical and Pharmacological Sciences
#14
JOURNAL ARTICLE
Hasan Cagri Yildirim, Caner Kapar, Baris Koksal, Mustafa Seyyar, Pervin Can Sanci, Murad Guliyev, Perihan Perkin, Mustafa Buyukkor, Sendag Yaslikaya, Nargiz Majidova, Merve Keskinkilic, Duygu Ozaskin, Tugay Avci, Tugce Kubra Gunes, Murat Arcagok, Alper Topal, Gul Sema Yildiran Keskin, Gozde Kavgaci, Nilgun Yildirim, Ozde Melisa Celayir, Nilufer Avci, Ferit Aslan, Ali Alkan, Mert Erciyestepe, Muhammet Cengiz, Metin Pehlivan, Ahmet Gulmez, Ismail Beypinar, Tugba Basoglu Tuylu, Erkan Kayikcioglu, Elvin Chalabiyev, Serdal Turhal, Halil Goksel Guzel, Eyyup Ayas, Mustafa Sahbazlar, Ozgecan Dulgar, Hacer Demir, Tugba Yavuzsen, Vedat Bayoglu, Derya Kivrak Salim, Banu Ozturk, Feyyaz Ozdemir, Oguz Kara, Berna Oksuzoglu, Oznur Bal, Nebi Serkan Demirci, Mesut Yilmaz, Devrim Cabuk, Sercan Aksoy
The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival...
March 18, 2024: Journal of Chemotherapy
#15
JOURNAL ARTICLE
Federica Miglietta, Letizia Pontolillo, Carmine De Angelis, Roberta Caputo, Monica Marino, Emilio Bria, Rossana Di Rienzo, Annarita Verrazzo, Carlo Buonerba, Giampaolo Tortora, Giuseppe Di Lorenzo, Lucia Del Mastro, Mario Giuliano, Filippo Montemurro, Fabio Puglisi, Valentina Guarneri, Michelino De Laurentiis, Luca Scafuri, Grazia Arpino
BACKGROUND: The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials. METHODS: We conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC. RESULTS: We selected 51 phase III trials...
March 9, 2024: Breast: Official Journal of the European Society of Mastology
#16
JOURNAL ARTICLE
M L Frevert, D Dannehl, L Jansen, S Hermann, H Schäffler, S Huwer, W Janni, I Juhasz-Böss, A D Hartkopf, F-A Taran
BACKGROUND: Following the positive iDFS and OS results of the phase III clinical trials monarchE, NATALEE and OlympiA, new oral anticancer agents (the CDK4/6 inhibitors abemaciclib, ribociclib as well as the PARP inhibitor olaparib) have recently been introduced into the treatment of high-risk early breast cancer (eBC). However, only few male patients were included in these trials (0.4%, 0.6% and 0.3%, respectively). The objective of this real-world analysis was to determine the proportion of male patients with eBC fulfilling the clinical high-risk criteria of above-mentioned trials...
March 12, 2024: Archives of Gynecology and Obstetrics
#17
JOURNAL ARTICLE
Adina Turcu-Stiolica, Ion Udristoiu, Mihaela-Simona Subtirelu, Victor Gheorman, Madalina Aldea, Elena Adriana Dumitrescu, Simona Ruxandra Volovat, Dragos Mircea Median, Cristian Virgil Lungulescu
Introduction: It is imperative for patients to respect the prescribed treatments to achieve the anticipated clinical outcomes, including the outpatients receiving oral anti-cancer drugs such as selective cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). With the introduction of three CDK 4/6i drugs in the Romanian pharmaceutical market in 2018, our study aimed to evaluate medication adherence and the influencing factors among patients undergoing treatment with palbociclib, ribociclib, or abemaciclib for advanced or metastatic breast cancer...
2024: Frontiers in Pharmacology
#18
REVIEW
Riccardo Gerosa, Rita De Sanctis, Flavia Jacobs, Chiara Benvenuti, Mariangela Gaudio, Giuseppe Saltalamacchia, Rosalba Torrisi, Giovanna Masci, Chiara Miggiano, Francesco Agustoni, Paolo Pedrazzoli, Armando Santoro, Alberto Zambelli
Aberrant cyclin-dependent kinase 2 (CDK2) activation has been identified as a main resistance mechanism to CDK4/6 inhibition in hormone-receptor positive (HR+) breast cancer. Additionally, consistent preclinical evidence states its crucial role in MYC and CCNE1 overexpressed cancer survival, such as triple-negative breast cancers (TNBC), thus representing an appealing and relatively unexplored target treatment opportunity. Despite emerging initial results of novel CDK2 inhibitors (CDK2i) activity, a comprehensive outcomes collection is currently absent from the scientific literature...
March 8, 2024: Critical Reviews in Oncology/hematology
#19
JOURNAL ARTICLE
Adam M Kase, Justyna Gleba, James L Miller, Erin Miller, Joachim Petit, Michael T Barrett, Yumei Zhou, Ephraim E Parent, Hancheng Cai, Joshua A Knight, Jacob Orme, Jordan Reynolds, William F Durham, Thomas M Metz, Nathalie Meurice, Brandy Edenfield, Aylin Alasonyalilar Demirer, Ahmet Bilgili, Peyton G Hickman, Matthew L Pawlush, Laura Marlow, Daniel P Wickland, Winston Tan, John A Copland
Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive malignancy with poor outcomes. To investigate novel therapeutic strategies, we characterized three new metastatic prostate cancer PDTX models and developed 3D spheroids from each to investigate molecular targeted therapy combinations including CDK4/6 inhibitors (CDK4/6i) with AKT inhibitors (ATKi). Metastatic prostate cancer tissue was collected and three PDTX models were established and characterized using WES. PDTX 3-D spheroids were developed from these three PDTXs to show resistance patterns and test novel molecular targeted therapies...
March 6, 2024: Molecular Cancer Therapeutics
#20
JOURNAL ARTICLE
Kadriye Bir Yücel, Uguray Aydos, Osman Sütcüoglu, Atiye Cenay Karabörk Kılıç, Nuriye Özdemir, Ahmet Özet, Ozan Yazıcı
PURPOSE: We aimed to investigate whether visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA) index are predictive for efficacy and hematological toxicity in ER + HER2-metastatic breast cancer (BC) patients who received CDK 4/6 inhibitors. METHODS: This retrospective cohort study analyzed 52 patients who were treated with CDK 4/6 inhibitors between January 2018 and February 2021. The values of VAT, SAT, SMA indices and hematological parameters were noted before the start, at the third and sixth months of this treatment...
March 4, 2024: Cancer Chemotherapy and Pharmacology
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