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Etienne Brain, Connie Chen, Sofia Simon, Vinay Pasupuleti, Kathleen Vieira Pfitzer, Karen A Gelmon
BACKGROUND: Palbociclib in combination with endocrine therapy is approved for treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. In addition to clinical trials, several real-world studies have evaluated the effectiveness of palbociclib. With increased life expectancy in the general population, breast cancer in older women is also expected to increase. OBJECTIVE: The aim was to systematically review evidence from both clinical trials and real-world studies for palbociclib treatment outcomes in older patients with HR+/HER2- advanced/metastatic breast cancer (a/mBC)...
March 28, 2024: Targeted Oncology
#22
JOURNAL ARTICLE
Chengfeng Bi, Yuhua Huang, Roshia Ali, Fang Wang, Xia Yang, Alyssa Bouska, Lu Xu, Xinbao Hao, Matthew A Lunning, Wing C Chan, Javeed Iqbal, Dennis D Weisenburger, Julie M Vose, Kai Fu
The current clinical management of Extranodal NK/T-cell lymphoma (ENKTL) primarily depends on conventional chemotherapy and radiotherapy, underscoring the need for innovative therapeutic strategies. This study explores the clinical significance and therapeutic implication of c-MYC (MYC) in ENKTL. Initially, we identified MYC protein overexpression in approximately 75% of cases within a large cohort of 111 patients. MYC overexpression was strongly correlated with lymphoma cell proliferation and poor clinical outcomes...
March 28, 2024: Haematologica
#23
JOURNAL ARTICLE
Ruichen Li, Qi Wang, Yang Zhao, Yi Zhu, Xiaoshen Wang
BACKGROUND: In head and neck squamous cell carcinoma (HNSCC) with human papillomavirus (HPV)-negative, deregulation of cell cycle is partly due to inactivation of p16INK4 and overexpression of cyclin D1. Here we investigated the in vitro and in vivo effects of the CDK4/6 inhibitor Palbociclib alone or combined with EGFR inhibitor Cetuximab in HNSCC. METHODS AND RESULTS: CCK-8, soft agar assay, colony formation assay, wound healing assay and transwell assay, β-galactosidase assay, western blotting, and cell-derived xenografts were used to investigated the in vitro and in vivo activity of drugs...
March 27, 2024: Molecular Biology Reports
#24
REVIEW
Adam Brufsky, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Rachel M Layman, Hope S Rugo
WHAT IS THIS SUMMARY ABOUT?: This summary describes an article published in the medical journal Frontiers in Oncology in September 2023. The article reports results from a study that looked at breast cancer treatments for older patients aged 75 years or older. The study focused on a type of cancer called HR+/HER2- metastatic breast cancer. HR+/HER2- stands for hormone receptorpositive/human epidermal growth factor receptor 2-negative. This study evaluated whether older patients with this type of cancer benefited from the combination of two medicines - palbociclib and an aromatase inhibitor - compared with taking an aromatase inhibitor alone...
March 27, 2024: Future Oncology
#25
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
#26
REVIEW
Hope S Rugo, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Rachel M Layman, Tiah Tomlin-Harris, Adam Brufsky
WHAT ARE THE KEY TAKEAWAYS?: This study used de-identified medical information from the Flatiron Database. This database contains healthcare information on people with cancer treated by doctors in the United States but personal information is removed to maintain privacy. Medical information for people who received certain treatments in routine clinical practice or real-world setting was included in the study. This study showed that in the real-world setting, African-Americans with HR+/HER2- MBC lived longer when receiving palbociclib with an AI than with an AI alone...
March 22, 2024: Future Oncology
#27
JOURNAL ARTICLE
Shaghayegh Saharkhiz, Negar Nasri, Nazanin Naderi, Ghasem Dini, Saeid Shirzadi Ghalehshahi, Fateme Firoozbakht
In this study, we present a targeted and pH-sensitive niosomal (pHSN) formulation, incorporating quantum dot (QD)-labeled Trastuzumab (Trz) molecules for the specific delivery of Palbociclib (Pal) to cells overexpressing human epidermal growth factor receptor 2 (HER2). FTIR analyses confirmed the successful preparation of the pHSNs and their bioconjugation. The labeled Trz-conjugated Pal-pHSNs (Trz-Pal-pHSNs) exhibited a size of approximately 170 nm, displaying a spherical shape with a neutral surface charge of -1...
June 2024: International journal of pharmaceutics: X
#28
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
#29
JOURNAL ARTICLE
Linhui Hu, Qian Li, Jiyu Wang, Huiping Wang, Xiyang Ren, Keke Huang, Yangyang Wang, Xue Liang, Lianfang Pu, Shudao Xiong, Zhimin Zhai
Differentiation therapy based on ATRA almost cured acute promyelocytic leukemia (APL). However, it is disappointing that ATRA is not effective against other acute myeloid leukemia (AML) subtypes. Developing new and effective anti-AML therapies that promote leukemia differentiation is necessary. The CDK4/6-cyclin D pathway is a key initiator of the G1/S phase transition, which determines cell fate. Herein, we investigated whether the CDK4/6 inhibitor palbociclib would synergize with ATRA to promote leukemia differentiation in vitro and in vivo...
March 20, 2024: Molecular Cancer Therapeutics
#30
JOURNAL ARTICLE
Xiaoqian Zhang, Ling Jin, Chenchen Zhou, Jinghua Liu, Qin Jiang
AIMS: This study aimed to improve personalized treatment strategies and predict survival outcomes for patients with uveal melanoma (UM). BACKGROUND: Copy number aberrations (CNAs) have been considered as a main feature of metastatic UM. OBJECTIVE: This study was designed to explore the feasibility of using copy number variation (CNV) in UM classification, prognosis stratification and treatment response. METHODS: The CNV data in the TCGA-UVM cohort were used to classify the samples...
March 19, 2024: Current Medicinal Chemistry
#31
JOURNAL ARTICLE
Jorge Gómez Tejeda Zañudo, Romualdo Barroso-Sousa, Esha Jain, Qingchun Jin, Tianyu Li, Jorge E Buendia-Buendia, Alyssa Pereslete, Daniel L Abravanel, Arlindo R Ferreira, Eileen Wrabel, Karla Helvie, Melissa E Hughes, Ann H Partridge, Beth Overmoyer, Nancy U Lin, Nabihah Tayob, Sara M Tolaney, Nikhil Wagle
The landscape of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) resistance is still being elucidated and the optimal subsequent therapy to overcome resistance remains uncertain. Here we present the final results of a phase Ib/IIa, open-label trial (NCT02871791) of exemestane plus everolimus and palbociclib for CDK4/6i-resistant metastatic breast cancer. The primary objective of phase Ib was to evaluate safety and tolerability and determine the maximum tolerated dose/recommended phase II dose (100 mg palbociclib, 5 mg everolimus, 25 mg exemestane)...
March 19, 2024: Nature Communications
#32
JOURNAL ARTICLE
Krishna C Aluri, Marina Slavsky, Ying Tan, Andrea Whitcher-Johnstone, Zhoupeng Zhang, Niresh Hariparsad, Diane Ramsden
Aminobenzotriazole (ABT) is commonly used as a non-selective inhibitor of cytochrome P450 (CYP) enzymes to assign contributions of CYP versus non-CYP pathways to the metabolism of new chemical entities. Despite widespread use, a systematic review of the drug-drug interaction (DDI) potential for ABT has not been published nor have the implications for using it in plated hepatocyte models for low clearance reaction phenotyping. The goal being to investigate the utility of ABT as a pan-CYP inhibitor for reaction phenotyping of low clearance compounds by evaluating stability over the incubation period, inhibition potential against UGT and sulfotransferase enzymes, and interaction with nuclear receptors involved in the regulation of drug metabolizing enzymes and transporters...
March 2024: Clinical and Translational Science
#33
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
#34
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
#35
JOURNAL ARTICLE
Cathy M Jacobs, Julia C Radosa, Lea Wagmann, Julia S M Zimmermann, Askin C Kaya, Aylin Aygün, Tatjana Edel, Lisa Stotz, Mohamed Ismaeil, Erich-Franz Solomayer, Markus R Meyer
Oral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side effects. Therefore, adherence to OET is an important issue and of high clinical significance for breast cancer patients' caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and high-resolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four different biomatrices (plasma, urine, finger prick blood by volumetric absorptive microsampling (VAMS), oral fluid (OF)) were evaluated regarding their suitability for AM of the OET abemaciclib, anastrozole, exemestane, letrozole, palbociclib, ribociclib, tamoxifen, and endoxifen...
March 15, 2024: Analytical and Bioanalytical Chemistry
#36
JOURNAL ARTICLE
Yu Yan, Bin Wu, Ling Wang
BACKGROUND: The aim of this study was to evaluate the association between CDK4/6 inhibitors and QT interval prolongation (QTp) and Torsades de Pointes (TdP) in breast cancer patients. METHOD: The cases with breast cancer from 2015 to 2022 were extracted from the FDA adverse event database (FARES) and further divided into a CDK4/6 inhibitor group and a positive control group. The associations between CDK4/6 inhibitors and QTp and TdP adverse events were evaluated using the reporting odds ratio (ROR) and the information component (IC)...
March 14, 2024: Expert Opinion on Drug Safety
#37
JOURNAL ARTICLE
Nahid Sultana, Howard L Elford, Jesika S Faridi
A hallmark of cancer is the dysregulation of the cell cycle. The CDK4/6 inhibitor palbociclib is approved for treating advanced estrogen-receptor-positive breast cancer, but its success is limited by the development of acquired resistance owing to long-term therapy despite promising clinical outcomes. This situation necessitates the development of potential combination strategies. Here, we report that didox, an inhibitor of ribonucleotide reductase in combination with palbociclib, can overcome palbociclib resistance in ER-positive and ER-negative breast cancers...
February 28, 2024: Cancers
#38
JOURNAL ARTICLE
Hua He, Lu Liang, Shiyao Jiang, Yueying Liu, Jingjing Huang, Xiaoyan Sun, Yi Li, Yiqun Jiang, Li Cong
Temozolomide (TMZ), a DNA alkylating agent, has become the primary treatment for glioma, the most common malignancy of the central nervous system. Although TMZ-containing regimens produce significant clinical response rates, some patients inevitably suffer from inferior treatment outcomes or disease relapse, likely because of poor chemosensitivity of glioma cells due to a robust DNA damage response (DDR). GINS2, a subunit of DNA helicase, contributes to maintaining genomic stability and is highly expressed in various cancers, promoting their development...
March 11, 2024: Cell Death & Disease
#39
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
#40
JOURNAL ARTICLE
Shoko Yao, Takanori Goi, Mizuho Takahashi, Hiroko Kono, Shigehiro Yokoi, Hiroyuki Maeda
A 52-year-old woman was presented with abdominal distension. Chest-abdominal CT showed some tumors in the left breast, enlarged axillary lymph nodes, ovary metastasis peritoneal thickening, a large amount of ascites. The diagnosis of needle biopsy in the breast mass was invasive ductal carcinoma, Luminal A type. The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Also chest and abdominal CT showed reduction of all lesions. We found the high expression of cyclin D1 protein and the negative of p16 protein in tissues of the needle biopsy...
February 2024: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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