5 results on '"Zakrzewska, Małgorzata"'
Search Results
2. The cytotoxic conjugate of highly internalizing tetravalent antibody for targeting FGFR1-overproducing cancer cells
- Author
-
Poźniak, Marta, Porębska, Natalia, Krzyścik, Mateusz Adam, Sokołowska-Wędzina, Aleksandra, Jastrzębski, Kamil, Sochacka, Martyna, Szymczyk, Jakub, Zakrzewska, Małgorzata, Otlewski, Jacek, and Opaliński, Łukasz
- Published
- 2021
- Full Text
- View/download PDF
3. Targeting Cellular Trafficking of Fibroblast Growth Factor Receptors as a Strategy for Selective Cancer Treatment.
- Author
-
Porębska, Natalia, Latko, Marta, Kucińska, Marika, Zakrzewska, Małgorzata, Otlewski, Jacek, and Opaliński, Łukasz
- Subjects
FIBROBLAST growth factor receptors ,CHIMERIC proteins ,GROWTH factors ,CELL membranes ,FIBROBLAST growth factors - Abstract
Fibroblast growth factor receptors (FGFRs) in response to fibroblast growth factors (FGFs) transmit signals across the cell membrane, regulating important cellular processes, like differentiation, division, motility, and death. The aberrant activity of FGFRs is often observed in various diseases, especially in cancer. The uncontrolled FGFRs' function may result from their overproduction, activating mutations, or generation of FGFRs' fusion proteins. Besides their typical subcellular localization on the cell surface, FGFRs are often found inside the cells, in the nucleus and mitochondria. The intracellular pool of FGFRs utilizes different mechanisms to facilitate cancer cell survival and expansion. In this review, we summarize the current stage of knowledge about the role of FGFRs in oncogenic processes. We focused on the mechanisms of FGFRs' cellular trafficking—internalization, nuclear translocation, and mitochondrial targeting, as well as their role in carcinogenesis. The subcellular sorting of FGFRs constitutes an attractive target for anti-cancer therapies. The blocking of FGFRs' nuclear and mitochondrial translocation can lead to the inhibition of cancer invasion. Moreover, the endocytosis of FGFRs can serve as a tool for the efficient and highly selective delivery of drugs into cancer cells overproducing these receptors. Here, we provide up to date examples how the cellular sorting of FGFRs can be hijacked for selective cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
4. Galectins as modulators of receptor tyrosine kinases signaling in health and disease.
- Author
-
Porębska, Natalia, Poźniak, Marta, Matynia, Aleksandra, Żukowska, Dominika, Zakrzewska, Małgorzata, Otlewski, Jacek, and Opaliński, Łukasz
- Subjects
- *
GALECTINS , *CARRIER proteins , *KINASES , *TYROSINE , *POST-translational modification , *LECTINS , *GLYCOCALYX - Abstract
[Display omitted] • Receptor tyrosine kinases (RTKs) regulate pivotal cellular processes and are dysregulated in cancer. • RTKs are extensively glycosylated and this modification affects cellular functions of these receptors. • Galectins are carbohydrate binding proteins implicated in developmental processes and cancers. Galectins directly and indirectly affect RTKs, modulating RTKs activation, their cross-talk with other cell surface proteins and their cellular trafficking. • Galectins are responsible for oncogenic activation of RTKs. • RTK-galectin interplay constitutes an attractive target for development of anti-cancer therapies. Receptor tyrosine kinases (RTKs) constitute a large group of cell surface proteins that mediate communication of cells with extracellular environment. RTKs recognize external signals and transfer information to the cell interior, modulating key cellular activities, like metabolism, proliferation, motility, or death. To ensure balanced stream of signals the activity of RTKs is tightly regulated by numerous mechanisms, including receptor expression and degradation, ligand specificity and availability, engagement of co-receptors, cellular trafficking of the receptors or their post-translational modifications. One of the most widespread post-translational modifications of RTKs is glycosylation of their extracellular domains. The sugar chains attached to RTKs form a new layer of information, so called glyco-code that is read by galectins, carbohydrate binding proteins. Galectins are family of fifteen lectins implicated in immune response, inflammation, cell division, motility and death. The versatility of cellular activities attributed to galectins is a result of their high abundance and diversity of their cellular targets. A various sugar specificity of galectins and the differential ability of galectin family members to form oligomers affect the spatial distribution and the function of their cellular targets. Importantly, galectins and RTKs are tightly linked to the development, progression and metastasis of various cancers. A growing number of studies points on the close cooperation between RTKs and galectins in eliciting specific cellular responses. This review focuses on the identified complexes between galectins and RTK members and discusses their relevance for the cell physiology both in healthy tissues and in cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. Multivalent protein-drug conjugates – An emerging strategy for the upgraded precision and efficiency of drug delivery to cancer cells.
- Author
-
Porębska, Natalia, Ciura, Krzysztof, Chorążewska, Aleksandra, Zakrzewska, Małgorzata, Otlewski, Jacek, and Opaliński, Łukasz
- Subjects
- *
CANCER cells , *TREATMENT effectiveness , *ANTINEOPLASTIC agents , *ANTIBODY-drug conjugates , *MOLECULAR structure , *NANOMEDICINE , *MONOCLONAL antibodies - Abstract
With almost 20 million new cases per year, cancer constitutes one of the most important challenges for public health systems. Unlike traditional chemotherapy, targeted anti-cancer strategies employ sophisticated therapeutics to precisely identify and attack cancer cells, limiting the impact of drugs on healthy cells and thereby minimizing the unwanted side effects of therapy. Protein drug conjugates (PDCs) are a rapidly growing group of targeted therapeutics, composed of a cancer-recognition factor covalently coupled to a cytotoxic drug. Several PDCs, mainly in the form of antibody-drug conjugates (ADCs) that employ monoclonal antibodies as cancer-recognition molecules, are used in the clinic and many PDCs are currently in clinical trials. Highly selective, strong and stable interaction of the PDC with the tumor marker, combined with efficient, rapid endocytosis of the receptor/PDC complex and its subsequent effective delivery to lysosomes, is critical for the efficacy of targeted cancer therapy with PDCs. However, the bivalent architecture of contemporary clinical PDCs is not optimal for tumor receptor recognition or PDCs internalization. In this review, we focus on multivalent PDCs, which represent a rapidly evolving and highly promising therapeutics that overcome most of the limitations of current bivalent PDCs, enhancing the precision and efficiency of drug delivery to cancer cells. We present an expanding set of protein scaffolds used to generate multivalent PDCs that, in addition to folding into well-defined multivalent molecular structures, enable site-specific conjugation of the cytotoxic drug to ensure PDC homogeneity. We provide an overview of the architectures of multivalent PDCs developed to date, emphasizing their efficacy in the targeted treatment of various cancers. • Protein-drug conjugates, PDCs, deliver a cytotoxic payload to cancer cells, leading to their death. • Multivalent PDCs are highly promising therapeutics characterized by increased precision and efficiency of drug delivery. • Protein scaffolds allow for the development of homogenous multivalent PDCs of diversified, well-defined architectures. • The modularity of protein scaffolds allows for rapid adaptation of PDCs to novel cancer-relevant targets. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.