Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity
| العنوان: | Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity |
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| المؤلفون: | Giuliana Cassinelli, Cinzia Lanzi |
| المصدر: | Molecules, Vol 23, Iss 11, p 2915 (2018) Molecules |
| بيانات النشر: | MDPI AG, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, heparan sulfate mimetics, heparan sulfate proteoglycan, Pharmaceutical Science, Review, heparin, Analytical Chemistry, heparanase, lcsh:QD241-441, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Growth factor receptor, lcsh:Organic chemistry, Biomimetic Materials, Neoplasms, non-anticoagulant heparin derivatives, Drug Discovery, medicine, Animals, Humans, Structure–activity relationship, Receptors, Growth Factor, Heparanase, Physical and Theoretical Chemistry, Cell Proliferation, Glucuronidase, Tumor microenvironment, Chemistry, Organic Chemistry, Heparin, Heparan sulfate, 030104 developmental biology, Mechanism of action, Chemistry (miscellaneous), Disease Progression, Selectins, Cancer research, Molecular Medicine, cancer therapy, Heparitin Sulfate, medicine.symptom, Selectin, Signal Transduction, medicine.drug |
| الوصف: | Beyond anticoagulation, the therapeutic potential of heparin derivatives and heparan sulfate (HS) mimetics (functionally defined HS mimetics) in oncology is related to their ability to bind and modulate the function of a vast array of HS-binding proteins with pivotal roles in cancer growth and progression. The definition of structural/functional determinants and the introduction of chemical modifications enabled heparin derivatives to be identified with greatly reduced or absent anticoagulant activity, but conserved/enhanced anticancer activity. These studies paved the way for the disclosure of structural requirements for the inhibitory effects of HS mimetics on heparanase, selectins, and growth factor receptor signaling, as well as for the limitation of side effects. Actually, HS mimetics affect the tumor biological behavior via a multi-target mechanism of action based on their effects on tumor cells and various components of the tumor microenvironment. Emerging evidence indicates that immunomodulation can participate in the antitumor activity of these agents. Significant ability to enhance the antitumor effects of combination treatments with standard therapies was shown in several tumor models. While the first HS mimetics are undergoing early clinical evaluation, an improved understanding of the molecular contexts favoring the antitumor action in certain malignancies or subgroups is needed to fully exploit their potential. |
| اللغة: | English |
| تدمد: | 1420-3049 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d96ef78173953a4a93bb5dc90112e9f https://www.mdpi.com/1420-3049/23/11/2915 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3d96ef78173953a4a93bb5dc90112e9f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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