Article
Multidisciplinary Sciences
Fabin Dang, Li Nie, Jin Zhou, Kouhei Shimizu, Chen Chu, Zhong Wu, Anne Fassl, Shizhong Ke, Yuangao Wang, Jinfang Zhang, Tao Zhang, Zhenbo Tu, Hiroyuki Inuzuka, Piotr Sicinski, Adam J. Bass, Wenyi Wei
Summary: Inhibition of CK1 epsilon can prevent acquisition of CDK4/6i resistance, enhancing the therapeutic efficacy of CDK4/6i in human breast cancer.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Mridula A. George, Sadaf Qureshi, Coral Omene, Deborah L. Toppmeyer, Shridar Ganesan
Summary: Targeted therapies such as CDK 4/6 inhibitors like palbociclib, ribociclib, and abemaciclib have improved the prognosis of metastatic HR positive breast cancer patients. While these three agents share overall similarities in CDK4/6 inhibition, there may be differences that explain unique clinical scenarios in which they are used.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
William D. Sinclair, Xiaoyan Cui
Summary: We investigated the effects of HER2 on CDK4/6 activity by assessing pRb levels in HER2-positive breast cancer. Our study suggests that HER2-positive breast cancer may potentially respond to CDK4/6 inhibitors, and pRb could be considered as a biomarker to predict the responsiveness.
CLINICAL BREAST CANCER
(2022)
Article
Multidisciplinary Sciences
Marta Palafox, Laia Monserrat, Meritxell Bellet, Guillermo Villacampa, Abel Gonzalez-Perez, Mafalda Oliveira, Fara Braso-Maristany, Nusaibah Ibrahimi, Srinivasaraghavan Kannan, Leonardo Mina, Maria Teresa Herrera-Abreu, Andreu Odena, Monica Sanchez-Guixe, Marta Capelan, Analia Azaro, Alejandra Bruna, Olga Rodriguez, Marta Guzman, Judit Grueso, Cristina Viaplana, Javier Hernandez, Faye Su, Kui Lin, Robert B. Clarke, Carlos Caldas, Joaquin Arribas, Stefan Michiels, Alicia Garcia-Sanz, Nicholas C. Turner, Aleix Prat, Paolo Nuciforo, Rodrigo Dienstmann, Chandra S. Verma, Nuria Lopez-Bigas, Maurizio Scaltriti, Monica Arnedos, Cristina Saura, Violeta Serra
Summary: CDK4/6 inhibitors combined with endocrine therapy show higher antitumor activity in the treatment of estrogen receptor-positive breast cancer. Overexpression of p16 is associated with reduced effectiveness of CDK4/6 inhibitors, while heterozygous RB1 loss is a biomarker of acquired resistance and poor clinical outcome. Combination of CDK4/6 inhibitor ribociclib with PI3K inhibitor alpelisib demonstrates antitumor activity regardless of specific mutations, even without endocrine therapy.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Abeer J. Al-Qasem, Carla L. Alves, Sidse Ehmsen, Martina Tuttolomondo, Mikkel G. Terp, Lene E. Johansen, Henriette Vever, Luna V. A. Hoeg, Daniel Elias, Martin Bak, Henrik J. Ditzel
Summary: The upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with resistance to AI monotherapy and combined CDK4/6i and ET in ER+ breast cancer. Co-targeting CDK2 and CDK4/6 along with ET synergistically impairs cellular growth, induces cell cycle arrest and apoptosis, and delays progression in resistant cell models.
NPJ PRECISION ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Edris Choupani, Zahra Madjd, Neda Saraygord-Afshari, Jafar Kiani, Arshad Hosseini
Summary: This study investigates the possibility of combining CDK4/6 inhibitor and AR inhibitor in AR-positive TNBC cells. The results show that this combination treatment has a good effect in inhibiting cell migration, clonogenic capacity, cell cycle progression, and cell growth, leading to improved therapeutic outcomes.
Article
Oncology
Miguel Gil-Gil, Emilio Alba, Joaquin Gavila, Juan de la Haba-Rodriguez, Eva Ciruelos, Pablo Tolosa, Daniele Candini, Antonio Llombart-Cussac
Summary: The article reviews the use of CDK4/6 inhibitors in the treatment of early breast cancer, including neoadjuvant and adjuvant settings. Evaluation of recent large phase 3 adjuvant trial results, examination of biomarkers as response predictive factors, and discussion on the combination of CDK4/6i and radiotherapy are included in the review.
Article
Medicine, General & Internal
Elisa Agostinetto, Veronique Debien, Guilherme Nader Marta, Matteo Lambertini, Martine Piccart-Gebhart, Evandro de Azambuja
Summary: The treatment landscape for HER2+ breast cancer is evolving rapidly, with CDK4/6 and PI3K inhibitors emerging as promising strategies to enhance patient outcomes. Data from preclinical and clinical studies are highlighting the potential of these agents in HER2+ disease and suggesting a potential shift in clinical practice.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2021)
Editorial Material
Biochemistry & Molecular Biology
Jose Manuel Perez-Garcia, Javier Cortes, Antonio Llombart-Cussac
Summary: The phase 3 study with dalpiciclib demonstrates the efficacy of CDK4/6 inhibitors in certain patients with metastatic breast cancer, providing valuable evidence for treatment decisions in the presence of multiple available inhibitors.
Article
Oncology
Luca Visani, Lorenzo Livi, Ivica Ratosa, Miha Orazem, Domen Ribnikar, Calogero Saieva, Carlotta Becherini, Viola Salvestrini, Erika Scoccimarro, Marianna Valzano, Cecilia Cerbai, Isacco Desideri, Marco Bernini, Lorenzo Orzalesi, Jacopo Nori, Simonetta Bianchi, Andrea Morandi, Icro Meattini
Summary: Through a retrospective analysis of data from 132 consecutive HR+/HER2- breast cancer patients, the study found no significant association between concurrent radiotherapy (RT) and adverse events (AEs) in patients treated with CDK4/6 inhibitors (CDK4/6i). Additionally, RT did not affect the dosage reduction or treatment discontinuation rates of CDK4/6i. The results highlight the safety of this combination therapy.
RADIOTHERAPY AND ONCOLOGY
(2022)
Article
Oncology
Xiuzhi Zhu, Li Chen, Binhao Huang, Xiaoguang Li, Liu Yang, Xin Hu, Yizhou Jiang, Zhimin Shao, Zhonghua Wang
Summary: The combination of PARPi olaparib and CDK4/6i palbociclib shows synergistic effects against BRCA(mut)/TNBC, especially in cells resistant to olaparib, by inhibiting HR repair, increasing DNA damage, and suppressing tumor growth.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Sibylle Loibl, Jenny Furlanetto
Summary: CDK4/6 inhibitors have a proven role in the treatment of breast cancer, delaying disease progression and improving survival. However, there are discrepancies in the results between early breast cancer and metastatic breast cancer studies, which require further investigation for clarification.
Article
Medicine, Research & Experimental
Ionut Marcel Cobec, Lavinia Moleriu, Aurica Elisabeta Moatar, Andreas Rempen
Summary: Therapy with CDK4/6 inhibitors in combination with AIs or fulvestrant has shown to be effective for hormone receptor-positive, HER2-negative breast cancer patients, with side effects and tumor response comparable to official data.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Oncology
Yingke Zhou, Xin Jin, Jian Ma, Donglin Ding, Zhenlin Huang, Haoyue Sheng, Yuqian Yan, Yunqian Pan, Ting Wei, Liguo Wang, Heshui Wu, Haojie Huang
Summary: This study reveals the interaction of HDAC5 and RB in cancer cells, showing that HDAC5 deficiency may result in resistance to CDK4/6 inhibitors, but this effect can be overcome by the BET-CBP/p300 dual inhibitor NEO2734.
Review
Oncology
Ilenia Migliaccio, Angela Leo, Francesca Galardi, Cristina Guarducci, Giulio Maria Fusco, Matteo Benelli, Angelo Di Leo, Laura Biganzoli, Luca Malorni
Summary: This review discusses recent achievements in the development of circulating biomarkers in patients with metastatic breast cancer treated with CDK4/6 inhibitors and endocrine therapy. Circulating biomarkers have the potential advantages of recognizing patients who might not respond to treatment and monitoring treatment effects with a simple withdrawal of peripheral blood.Various circulating markers are currently being tested for their potential to predict response to CDK4/6 inhibitors treatment in patients with HR+/HER2- breast cancer.
Article
Oncology
Vera Mugoni, Yari Ciani, Caterina Nardella, Francesca Demichelis
Summary: The identification of prostate cancer biomarkers in patients' blood and urine can significantly improve PCa diagnosis and monitoring. Using EV-RNAs as biomarkers in PCa shows great potential, but faces challenges of EV heterogeneity and complexity.
Article
Biochemistry & Molecular Biology
Yari Ciani, Tarcisio Fedrizzi, Davide Prandi, Francesca Lorenzin, Alessio Locallo, Paola Gasperini, Gian Marco Franceschini, Matteo Benelli, Olivier Elemento, Luca L. Fava, Alberto Inga, Francesca Demichelis
Summary: Pan-cancer studies have provided insights into the genomic landscape of various tumor types. By analyzing allele-specific data from the Cancer Genome Atlas (TCGA), this study reclassified copy-number variations and revealed associations between driver mutations and loss of heterozygosity (LOH). Integration of allele-specific genomics and transcriptomics highlighted the relevance of allele-specific gene status in the regulation of TP53 and its targets. Furthermore, the study identified the role of copy-neutral LOH in the impairment of tumor suppressor genes and disease progression.
Article
Oncology
Ilenia Migliaccio, Marta Paoli, Emanuela Risi, Chiara Biagioni, Laura Biganzoli, Matteo Benelli, Luca Malorni
Summary: This study aims to investigate the prognostic value of PIK3CA mutations and copy number gain in hormone receptor-positive and HER2-negative breast cancer. Analysis of samples from three datasets revealed that 8-10% of patients had PIK3CA mutations and gain, which were associated with worse outcome. The clinical benefit of targeted treatment was found to be similar among patients with different mutation types.
Article
Oncology
Luca Malorni, Svitlana' Tyekucheva, Florentine S. Hilbers, Michail Ignatiadis, Patrick Neven, Marco Colleoni, Stephanie Henry, Alberto Ballestrero, Andrea Bonetti, Guy Jerusalem, Konstantinos Papadimitriou, Antonio Bernardo, Elena Seles, Francois P. Duhoux, Iain R. MacPherson, Alastair Thomson, David Mark Davies, Mattias Bergqvist, Ilenia Migliaccio, Geraldine Gebhart, Gabriele Zoppoli, Judith M. Bliss, Matteo Benelli, Amelia McCartney, Roswitha Kammler, Heidi De Swert, Barbara Ruepp, Debora Fumagalli, Rudolf Maibach, David Cameron, Sherene Loi, Martine Piccart, Meredith M. Regan
Summary: This study investigated the prognostic role of serum thymidine kinase activity (sTKa) in patients with metastatic breast cancer treated with Palbociclib + fulvestrant. The results showed that the changes in sTKa levels during treatment were closely associated with patients' progression-free survival, and high pre-treatment sTKa levels and incomplete suppression during treatment may identify patients with poorer prognosis and primary resistance.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Immunology
Luca Pangrazzi, Sacha Genovesi, Luigi Balasco, Enrica Cerilli, Camilla Robol, Giulia Zunino, Silvano Piazza, Giovanni Provenzano, Yuri Bozzi
Summary: This study investigates the association between immune dysfunction and cerebellar defects in autism spectrum disorder. The cerebellar transcriptome of En2(-/-) mice shows over-representation of biological processes related to immune function, while pro-inflammatory molecules are reduced in the cerebellum and increased in the peripheral blood of mutant mice.
JOURNAL OF NEUROIMMUNOLOGY
(2022)
Article
Cell Biology
Michela Sgubin, Silvia Pegoraro, Ilenia Pellarin, Gloria Ros, Riccardo Sgarra, Silvano Piazza, Gustavo Baldassarre, Barbara Belletti, Guidalberto Manfioletti
Summary: This study reveals a new interaction mechanism involving High Mobility Group A1 (HMGA1) in breast cancer cell migration, and suggests that low levels of HMGA1 may enhance the effectiveness of certain drug treatments.
CELL DEATH & DISEASE
(2022)
Correction
Multidisciplinary Sciences
Mathys Grapotte, Manu Saraswat, Chloe Bessiere, Christophe Menichelli, Jordan A. Ramilowski, Jessica Severin, Yoshihide Hayashizaki, Masayoshi Itoh, Michihira Tagami, Mitsuyoshi Murata, Miki Kojima-Ishiyama, Shohei Noma, Shuhei Noguchi, Takeya Kasukawa, Akira Hasegawa, Harukazu Suzuki, Hiromi Nishiyori-Sueki, Martin C. Frith, Clement Chatelain, Piero Carninci, Michiel J. L. de Hoon, Wyeth W. Wasserman, Laurent Brehelin, Charles-Henri Lecellier
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Agostina Nardone, Xintao Qiu, Sandor Spisak, Zsuzsanna Nagy, Ariel Feiglin, Avery Feit, Gabriela Cohen Feit, Yingtian Xie, Alba Font-Tello, Cristina Guarducci, Francisco Hermida-Prado, Sudeepa Syamala, Klothilda Lim, Miguel Munoz Gomez, Matthew Pun, MacIntosh Cornwell, Weihan Liu, Aysegul Ors, Hisham Mohammed, Paloma Cejas, Jane B. Brock, Matthew L. Freedman, Eric P. Winer, Xiaoyong Fu, Rachel Schiff, Henry W. Long, Otto Metzger Filho, Rinath Jeselsohn
Summary: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor-positive. However, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, the researchers found that ILC had a unique chromatin state and FOXA1-ER axis that promoted tumor progression, offering a novel mechanism of tamoxifen resistance. These results highlight the importance of conducting clinical trials dedicated to patients with ILC to optimize treatments in this breast cancer subtype.
Article
Cell Biology
Chiara Volani, Alessandra Pagliaro, Johannes Rainer, Giuseppe Paglia, Benedetta Porro, Ilaria Stadiotti, Luisa Foco, Elisa Cogliati, Adolfo Paolin, Costanza Lagrasta, Caterina Frati, Emilia Corradini, Angela Falco, Theresa Matzinger, Anne Picard, Benedetta Ermon, Silvano Piazza, Marzia De Bortoli, Claudio Tondo, Reginald Philippe, Andrea Medici, Alexandros A. Lavdas, Michael J. F. Blumer, Giulio Pompilio, Elena Sommariva, Peter P. Pramstaller, Jakob Troppmair, Viviana Meraviglia, Alessandra Rossini
Summary: The study demonstrates the crucial role of GCN5 in arrhythmogenic cardiomyopathy, reducing lipid accumulation by modulating cellular redox balance pathways.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Elisa Focchi, Clara Cambria, Lara Pizzamiglio, Luca Murru, Silvia Pelucchi, Laura D'Andrea, Silvano Piazza, Lorenzo Mattioni, Maria Passafaro, Elena Marcello, Giovanni Provenzano, Flavia Antonucci
Summary: In this study, Atm(+/-) and Atm(-/-) mice were used to investigate the effects of the antidepressant Fluoxetine (Fluox) on cognitive defects. The results showed that Fluox specifically increased the levels of NKCC1 in the hippocampus, indicating a context-specificity of ATM. Further analysis revealed increased levels of kainate receptors (KARs) containing Gluk-1 and Gluk-5 subunits in the hippocampus of Atm(+/-) and Atm(-/-) mice. The study suggests that ATM affects both inhibitory and excitatory neurotransmission and may be involved in neurological and psychiatric disorders.
CELL DEATH & DISEASE
(2022)
Article
Biochemical Research Methods
Dario Romagnoli, Agostina Nardone, Francesca Galardi, Marta Paoli, Francesca De Luca, Chiara Biagioni, Gian Marco Franceschini, Marta Pestrin, Giuseppina Sanna, Erica Moretti, Francesca Demichelis, Ilenia Migliaccio, Laura Biganzoli, Luca Malorni, Matteo Benelli
Summary: DNA-methylation alterations are common in cancer and can be used as ideal markers for tumor quantification and classification. The computational framework MIMESIS utilizes minimal DNA-methylation signatures to accurately estimate tumor content and classify tumor type and molecular subtype in tissue and cell-free DNA samples. The study demonstrates the potential of MIMESIS in developing cost-effective and scalable DNA-methylation assays for precision oncology in clinical practice.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Sergio Alexandre Alcantara Santos, Luiz Marcos Frediani Portela, Ana Carolina Lima Camargo, Flavia Bessi Constantino, Ketlin Thassiani Colombelli, Matheus Naia Fioretto, Renato Mattos, Bruno Evaristo de Almeida Fantinatti, Michela Alessandra Denti, Silvano Piazza, Sergio Luis Felisbino, Elena Zambrano, Luis Antonio Justulin
Summary: This study describes the deregulation of two miRNAs in the prostate of rats born to dams fed with a low protein diet. Integrative analysis of transcriptomic and proteomic data reveals potential molecular mechanisms involved in prostate cancer. Imbalance of the testosterone/estrogen ratio in the offspring rats highlights the importance of improving maternal healthcare.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sara Petrosino, Sabrina Pacor, Silvia Pegoraro, Virginia Anna Gazziero, Giulia Canarutto, Silvano Piazza, Guidalberto Manfioletti, Riccardo Sgarra
Summary: Breast cancer is the leading cause of cancer death in women, and triple-negative breast cancer is the most aggressive subtype. HMGA1, an oncogenic factor, is involved in the development and progression of breast cancer. The study found that the RD-HIST gene expression is enriched in breast cancer tissues and correlates with HMGA1 expression. In TNBC cells, HMGA1 influences the expression of RD-HIST genes and interacts with NPAT. Silencing HMGA1 increases the percentage of cells in G0/G1 phase and reduces the efficacy of epirubicin treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Luca Malorni, Giampaolo Bianchini, Roberta Caputo, Alberto Zambelli, Fabio Puglisi, Giulia Bianchi, Lucia Del Mastro, Ida Paris, Filippo Montemurro, Giacomo Allegrini, Marco Colleoni, Stefano Tamberi, Claudio Zamagni, Marina E. Cazzaniga, Michele Orditura, Valentina Guarneri, Daniela Castelletti, Matteo Benelli, Mariacristina Di Marino, Grazia Arpino, Michelino De Laurentiis
Summary: In this study, it was found that serum TK1 activity (sTKa) can serve as a novel prognostic and pharmacodynamic biomarker in patients with HR+/HER2- ABC treated with ribociclib plus letrozole as first-line therapy.
EUROPEAN JOURNAL OF CANCER
(2023)