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The personalization of therapies in breast cancer has favoured the introduction of new molecular-targeted therapies into clinical practice. Among them, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have acquired increasing importance, with the approval in recent years of palbociclib, ribociclib, and abemaciclib in combination with endocrine therapy. Currently, no guidelines are available to monitor and manage potential long-term toxicities associated with the use of these drugs. A multidisciplinary panel of European oncologists, was supported by a pharmacologist, a hematologist, a hepatologist and a pulmonologist to discuss the management of long-term toxicities, based on the literature review and their clinical experience. The panel provided detailed roadmaps to manage long-term toxicities associated with the use of CDK4/6 inhibitors in clinical practice. Knowing the frequency and characteristics of the toxicity profile associated with each CDK4/6 inhibitor is important in the decision-making process to match the right drug to the right patient.
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http://dx.doi.org/10.3389/fonc.2023.1247270 | DOI Listing |
Bull Cancer
September 2025
Department of Pathology and Medical Biology, Cancer Genetics Laboratory, Gustave Roussy, Villejuif, France.
The effectiveness and tolerability of medicines can vary considerably from person to person, even at the same dose. This variation is influenced by many factors, including constitutional genetic characteristics. In fact, some people have genetic variations that are common and neutral in the population, known as polymorphisms, which can affect drug metabolism or make them more susceptible to certain adverse effects.
View Article and Find Full Text PDFArch Biochem Biophys
September 2025
Department of Hematology, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China 200433. Electronic address:
Background: Benzene, a ubiquitous industrial chemical, is a well-established environmental toxin associated with hematological disorders such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), which are characterized by impaired hematopoiesis and bone marrow failure. This study investigates the role of ferroptosis, an iron-dependent form of cell death, in benzene-induced hematotoxicity, focusing on the repression of glutathione peroxidase 4 (GPX4), a critical regulator of ferroptosis.
Materials And Methods: Male C57BL/6 mice were exposed to benzene at various doses over six weeks.
Biochim Biophys Acta Mol Cell Res
September 2025
University of Warsaw, Faculty of Biology, Institute of Experimental Plant Biology and Biotechnology, Department of Plant Metal Homeostasis, 1 Miecznikowa Str., 02-096, Warszawa, Poland. Electronic address:
The Natural Resistance Associated Macrophage Proteins (NRAMPs) are membrane-targeted transporters with low substrate specificity, that mediate the import (translocation to the cytoplasm) of metals, mainly essential nutrients, e.g. iron (Fe), manganese (Mn), zinc (Zn), cobalt (Co), copper (Cu) or nickel (Ni).
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell The
Despite its potential as a cancer immunotherapy, wild-type IL-2 is limited by dose-limiting toxicities, including vascular leak syndrome, and its strong activation of regulatory T cells (Tregs), which dampens anti-tumor immunity. These drawbacks are largely driven by IL-2's binding to IL-2Rα, and avoiding this interaction can reduce IL-2-associated toxicities, although it cannot completely eliminate them. To overcome these limitations, βγ-biased IL-2 variants (Non-α-IL-2) have been developed to selectively activate effector T and NK cells.
View Article and Find Full Text PDFPharmacol Ther
September 2025
Department of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address:
Air pollution is a significant public health issue that impacts lung health, particularly in vulnerable populations such as children, the elderly, and individuals with pre-existing respiratory conditions. Both natural and anthropogenic sources of air pollution give rise to a variety of toxic compounds, including particulate matter (PM), ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAHs). Exposure to these pollutants is strongly associated with the development and exacerbation of respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF).
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