Article
Chemistry, Medicinal
Huifang Shan, Xinyu Ma, Guoyi Yan, Meng Luo, Xinxin Zhong, Suke Lan, Jie Yang, Yuanyuan Liu, Chunlan Pu, Yu Tong, Rui Li
Summary: A series of covalent CDK4/6 inhibitors were designed and synthesized, with compound C-13 showing potent anticancer activity in vitro and significant tumor growth inhibition in a mouse model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Cell Biology
Mattia Garutti, Giada Targato, Silvia Buriolla, Lorenza Palmero, Alessandro Marco Minisini, Fabio Puglisi
Summary: Historically, metastatic melanoma was considered highly lethal, but recent drug developments have improved prognosis significantly. The use of BRAF/MEK inhibitors and anti-PD1 antibodies has revolutionized disease management. However, not all patients benefit from these therapies, leading to the need for new clinically active compounds to be tested in clinical trials.
Article
Biochemistry & Molecular Biology
Lisa Crozier, Reece Foy, Brandon L. Mouery, Robert H. Whitaker, Andrea Corno, Christos Spanos, Tony Ly, Jeanette Gowen Cook, Adrian T. Saurin
Summary: CDK4/6 inhibitors can induce a prolonged G1 arrest, downregulate replisome components, impair origin licencing, and lead to long-lasting effects on tumor growth. This unexpected ability to induce DNA damage provides a rationale for predicting responsive tumor types and effective combination therapies.
Review
Biochemistry & Molecular Biology
Valerio Nardone, Marcella Barbarino, Antonio Angrisani, Pierpaolo Correale, Pierpaolo Pastina, Salvatore Cappabianca, Alfonso Reginelli, Luciano Mutti, Clelia Miracco, Rocco Giannicola, Antonio Giordano, Luigi Pirtoli
Summary: The expanding clinical application of CDK4- and CDK6-inhibiting drugs in breast cancer has sparked interest in testing them in other tumors. Potential combinations with other therapeutic approaches are being explored, with some hypotheses about integrating CDK4 and CDK6 inhibitors with radiotherapy. However, more research is needed to further investigate the potential benefits of these combinations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Sabine Paternot, Eric Raspe, Clement Meiller, Maxime Tarabichi, Jean-Baptiste Assie, Frederick Libert, Myriam Remmelink, Xavier Bisteau, Patrick Pauwels, Yuna Blum, Nolwenn Le Stang, Severine Tabone-Eglinger, Francoise Galateau-Salle, Christophe Blanquart, Jan P. Van Meerbeeck, Thierry Berghmans, Didier Jean, Pierre P. Roger
Summary: This study evaluated the impact of CDK4/6 inhibition by palbociclib in malignant pleural mesothelioma (MPM) and found that MPM is uniquely sensitive to CDK4/6 inhibitors. Palbociclib can durably inhibit cell proliferation, even after drug washout, and induce a senescence-associated secretory phenotype. The study supports the evaluation of CDK4/6 inhibitors as monotherapy or combination therapy for MPM treatment.
MOLECULAR ONCOLOGY
(2022)
Article
Chemistry, Physical
Naila Zaman, Rimsha Yousaf, Zahra Akhtar, Syed Sikander Azam
Summary: In this study, nine different drug combinations targeting p27-CDK4/cyclin D1 complex were tested experimentally, and the most effective combinations were found to stabilize the active dimer. The study also highlighted the role of the p27 linker as well as environmental factors in drug efficacy.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Marian Kratzke, George Scaria, Stephen Porter, Betsy Kren, Mark A. Klein
Summary: Advanced mesothelioma is an incurable disease, and new treatment strategies are needed. This study demonstrated that the inhibitors auranofin and palbociclib could effectively decrease mesothelioma cell proliferation and inhibit activity related to antioxidant defense and cell cycle progression. Further investigation of this drug combination may reveal a new treatment strategy for mesothelioma.
Review
Chemistry, Multidisciplinary
Tenzin Adon, Dhivya Shanmugarajan, Honnavalli Yogish Kumar
Summary: The discovery of CDK4/6 inhibitors is considered a game-changer in cancer therapy, as their inhibition triggers cell cycle arrest and apoptosis. Targeting CDK4/6 has been proposed as a paradigm shift in anticancer approaches, and the development of effective inhibitors is becoming a promising cancer therapy.
Article
Oncology
Qing Li, Baishan Jiang, Jiaye Guo, Hong Shao, Isabella S. Del Priore, Qing Chang, Rei Kudo, Zhiqiang Li, Pedram Razavi, Bo Liu, Andrew S. Boghossian, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Katherine A. Donovan, Marta Palafox, Jorge S. Reis-Filho, Elisa de Stanchina, Eric S. Fischer, Neal Rosen, Violeta Serra, Andrew Koff, John D. Chodera, Nathanael S. Gray, Sarat Chandarlapaty
Summary: This study identifies CDK4/6 kinase activation as a common mechanism in oncogenic signaling-induced proliferation and develops a new strategy for inhibiting CDK4/6 kinases to overcome resistance.
Review
Oncology
Maxwell R. Lloyd, Laura M. Spring, Aditya Bardia, Seth A. Wander
Summary: CDK4/6 inhibitors have become the standard of care for patients with hormone receptor-positive advanced breast cancer. Research efforts have identified common resistance drivers and precision-guided therapeutic strategies are under development.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Swapna Asuthkar, Sujatha Venkataraman, Janardhan Avilala, Katherine Shishido, Rajeev Vibhakar, Bethany Veo, Ian J. Purvis, Maheedhara R. Guda, Kiran K. Velpula
Summary: Medulloblastoma (MB) is the most common malignant pediatric brain tumor, and the standard of care for MB patients includes maximum safe resection, postoperative craniospinal irradiation, and chemotherapy. Recent research has identified SMYD3 as a crucial epigenetic regulator, which activates the transcription of cyclin D3 and drives the growth of Group 3 Myc+ MB cells.
Article
Biochemistry & Molecular Biology
Betheney R. Pennycook, Alexis R. Barr
Summary: The use of CDK4/6 inhibitors in cancer treatment is a topic of ongoing investigation, with limited understanding of their mechanisms of action. Recent data have raised questions about how these inhibitors arrest cell proliferation, leading to renewed interest in the roles of CDK4/6. Studying the effects of CDK4/6 inhibitors on the cell cycle can have implications for cancer treatment and patient stratification.
Article
Oncology
Nitisha Shrivastava, Claudia Gutierrez Chavez, Daniel Li, Vikas Mehta, Carlos Thomas, Cory D. D. Fulcher, Nicole Kawachi, Danielle M. M. Bottalico, Michael B. B. Prystowsky, Indranil Basu, Chandan Guha, Thomas J. J. Ow
Summary: Human papilloma virus-negative (HPV(-)) oral cavity squamous cell carcinoma (OCSCC) is a major cause of death in head and neck cancers. Radiation resistance is a significant challenge in the treatment of OCSCC. This study investigated the potential of targeting the CDK4/6 pathway in HPV(-) OCSCC using palbociclib and its effect on radiation sensitivity.
Article
Biochemistry & Molecular Biology
Ravi K. Gupta, Petra Mlcochova
Summary: SARS-CoV-2 infection triggers redistribution of cyclin D1 and D3 from the nucleus to the cytoplasm, followed by proteasomal degradation. Cyclin D3 interacts with SARS-CoV-2 proteins and affects the assembly and release of newly produced virions, highlighting the importance of understanding the virus-host interactions.
Review
Oncology
Jinmeng Zhang, Dayu Xu, Yue Zhou, Zhengfei Zhu, Xi Yang
Summary: CDK4/6 inhibitors have shown potential as a new therapeutic agent for non-small cell lung cancer by preventing tumor cells from entering the G1 and S phases. Clinical studies have demonstrated some positive results, indicating the potential for future treatment options.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lingyun Dai, Tianyun Zhao, Xavier Bisteau, Wendi Sun, Nayana Prabhu, Yan Ting Lim, Radoslaw M. Sobota, Philipp Kaldis, Par Nordlund
Article
Biochemistry & Molecular Biology
Radoslaw Szmyd, Joanna Niska-Blakie, M. Kasim Diril, Patricia Renck Nunes, Konstantinos Tzelepis, Aurelie Lacroix, Noemi van Hul, Lih-Wen Deng, Joao Matos, Oliver Dreesen, Xavier Bisteau, Philipp Kaldis
Article
Cell Biology
Nathan Palmer, S. Zakiah A. Talib, Chandrahas Koumar Ratnacaram, Diana Low, Xavier Bisteau, Joanna Hui Si Lee, Elisabeth Pfeiffenberger, Heike Wollmann, Joel Heng Loong Tan, Sheena Wee, Radoslaw Sobota, Jayantha Gunaratne, Daniel M. Messerschmidt, Ernesto Guccione, Philipp Kaldis
JOURNAL OF CELL BIOLOGY
(2019)
Correction
Biochemistry & Molecular Biology
Radoslaw Szmyd, Joanna Niska-Blakie, M. Kasim Diril, Patricia Renck Nunes, Konstantinos Tzelepis, Aurelie Lacroix, Noemi van Hul, Lih-Wen Deng, Joao Matos, Oliver Dreesen, Xavier Bisteau, Philipp Kaldis
Article
Oncology
Gabrielle van Caloen, Sandra Schmitz, Mariama El Baroudi, Xavier Caignet, Sebastien Pyr Dit Ruys, Pierre P. Roger, Didier Vertommen, Jean-Pascal Machiels
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Biochemistry & Molecular Biology
Xavier Bisteau, Joann Lee, Vinayaka Srinivas, Joanna H. S. Lee, Joanna Niska-Blakie, Gifford Tan, Shannon Y. X. Yap, Kevin W. Hom, Cheng Kit Wong, Jeongjun Chae, Loo Chien Wang, Jinho Kim, Giulia Rancati, Radoslaw M. Sobota, Chris S. H. Tan, Philipp Kaldis
Article
Oncology
Gabrielle van Caloen, Sandra Schmitz, Cedric van Marcke, Xavier Caignet, Antonella Mendola, Sebastien Pyr Dit Ruys, Pierre P. Roger, Didier Vertommen, Jean-Pascal Machiels
Summary: The combination of cetuximab and ribociclib was not significantly more effective than cetuximab monotherapy in HPV-negative SCCHN patient-derived tumor xenograft (PDTX) models. In addition, the combination of cetuximab and ribociclib may reduce the activity of the CDK4/6 inhibitor in cetuximab-resistant models. The downregulation of the retinoblastoma (Rb) protein was observed in cetuximab-treated mice, suggesting potential mechanisms for cetuximab resistance.
Article
Biology
Juan Alfonso Redondo, Romain Bibes, Alizee Vercauteren Drubbel, Benjamin Dassy, Xavier Bisteau, Eleonore Maury, Benjamin Beck
Summary: The study focused on the oscillations of the clock-related gene PER2 in esophageal cancer cells and found that chemotherapy is more effective when PER2 expression is low. This suggests that chronotherapy could enhance the impact of current chemotherapy regimens for esophageal cancer. The results indicate that understanding and utilizing the circadian rhythm in cancer treatment may lead to improved therapeutic outcomes.
Article
Cell Biology
Katia Coulonval, Vincent Vercruysse, Sabine Paternot, Jaime M. Pita, Robert Corman, Eric Raspe, Pierre P. Roger
Summary: CDK4 is a key integrator coupling mitogenic/oncogenic signaling with cell division cycle, and the phosphorylation status at its T172 residue plays a critical role in determining the activity of CDK4 complexes, and predicting tumor cell sensitivity to drugs including palbociclib. Monoclonal antibodies specifically recognizing T172-phosphorylated CDK4 have been developed, facilitating the study of CDK4 phosphorylation and its interaction with other proteins.
Article
Anatomy & Morphology
Mireia Rovira, Magali Miserocchi, Alice Montanari, Latifa Hammou, Laura Chomette, Jennifer Pozo, Virginie Imbault, Xavier Bisteau, Valerie Wittamer
Summary: The fish-specific monoclonal antibody 4C4 was found to recognize Lgals3bpb, a protein that is present in microglial cells and leukocytes in the periphery including macrophages in the gut and liver.
DEVELOPMENTAL DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Angel Gonzalez-Valero, Audrey G. Reeves, Annika C. S. Page, Patrick J. Moon, Edward Miller, Katia Coulonval, Steven W. M. Crossley, Xiao Xie, Dan He, Patricia Z. Musacchio, Alec H. Christian, Jeffrey M. McKenna, Richard A. Lewis, Eric Fang, Dustin Dovala, Yipin Lu, Lynn M. McGregor, Markus Schirle, John A. Tallarico, Pierre P. Roger, F. Dean Toste, Christopher J. Chang
Summary: Activity-based protein profiling (ABPP) is a versatile strategy for identifying and characterizing functional protein sites and compounds for therapeutic development. This study introduces a methionine-specific ABPP platform and successfully identifies new ligandable methionine sites. The work also presents a unique therapeutic intervention method, laying the foundation for discovering and targeting previously undruggable methionine sites.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Oncology
Sabine Paternot, Eric Raspe, Clement Meiller, Maxime Tarabichi, Jean-Baptiste Assie, Frederick Libert, Myriam Remmelink, Xavier Bisteau, Patrick Pauwels, Yuna Blum, Nolwenn Le Stang, Severine Tabone-Eglinger, Francoise Galateau-Salle, Christophe Blanquart, Jan P. Van Meerbeeck, Thierry Berghmans, Didier Jean, Pierre P. Roger
Summary: This study evaluated the impact of CDK4/6 inhibition by palbociclib in malignant pleural mesothelioma (MPM) and found that MPM is uniquely sensitive to CDK4/6 inhibitors. Palbociclib can durably inhibit cell proliferation, even after drug washout, and induce a senescence-associated secretory phenotype. The study supports the evaluation of CDK4/6 inhibitors as monotherapy or combination therapy for MPM treatment.
MOLECULAR ONCOLOGY
(2022)
Review
Oncology
Tatjana Arsenijevic, Katia Coulonval, Eric Raspe, Anne Demols, Pierre P. Roger, Jean-Luc Van Laethem
Summary: Pancreatobiliary cancers have a low survival rate, and current treatments are not very effective. There is an urgent need for new therapeutic strategies. Recent evidence suggests that CDK4/6 inhibitors could be a promising treatment option for these types of cancers. This article discusses the potential of CDK4/6 inhibitors in treating cholangiocarcinoma and pancreatic ductal adenocarcinoma.
Article
Genetics & Heredity
Matthew R. Dewhurst, Jin Rong Ow, Gozde Zafer, Noemi K. M. van Hul, Heike Wollmann, Xavier Bisteau, David Brough, Hyungwon Choi, Philipp Kaldis