Cinzia Lanzi - Fondazione IRCCS Istituto Nazionale dei Tumori - Dr

Cinzia Lanzi

Fondazione IRCCS Istituto Nazionale dei Tumori

Dr

Milano, Lombardia | Italy

Main Specialties: Biology, Oncology, Pharmacology

Additional Specialties: experimental oncology

ORCID logohttps://orcid.org/0000-0002-4480-9413

Cinzia Lanzi - Fondazione IRCCS Istituto Nazionale dei Tumori - Dr

Cinzia Lanzi

Introduction

Primary Affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori - Milano, Lombardia , Italy

Specialties:

Additional Specialties:

Research Interests:

Experience

Fondazione IRCCS Istituto Nazionale dei Tumori

Publications

3Publications

142Reads

7Profile Views

Overactive IGF1/Insulin Receptors and NRASQ61R Mutation Drive Mechanisms of Resistance to Pazopanib and Define Rational Combination Strategies to Treat Synovial Sarcoma.

Cancers (Basel) 2019 Mar 22;11(3). Epub 2019 Mar 22.

Department of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy.

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Source
https://www.mdpi.com/2072-6694/11/3/408
Publisher Site
http://dx.doi.org/10.3390/cancers11030408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468361PMC
March 2019
104 Reads

Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity.

Molecules 2018 Nov 8;23(11). Epub 2018 Nov 8.

Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

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.

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http://www.mdpi.com/1420-3049/23/11/2915
Publisher Site
http://dx.doi.org/10.3390/molecules23112915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278363PMC
November 2018
21 Reads
2.416 Impact Factor

Targeting Heparan Sulfate Proteoglycans and their Modifying Enzymes to Enhance Anticancer Chemotherapy Efficacy and Overcome Drug Resistance.

Curr Med Chem 2017 ;24(26):2860-2886

Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Experimental Oncology and Molecular Medicine, Molecular Pharmacology Unit, via Amadeo 42, 20133 Milan. Italy.

Targeting heparan sulfate proteoglycans (HSPGs) and enzymes involved in heparan sulfate (HS) chain editing is emerging as a new anticancer strategy. The involvement of HSPGs in tumor cell signaling, inflammation, angiogenesis and metastasis indicates that agents able to inhibit aberrant HSPG functions can potentially act as multitarget drugs affecting both tumor cell growth and the supportive boost provided by the microenvironment. Moreover, accumulating evidence supports that an altered expression or function of HSPGs, or of the complex enzyme system regulating their activities, can also depress the tumor response to anticancer treatments in several tumor types. Thereby, targeting HSPGs or HSPG modifying enzymes appears an appealing approach to enhance chemotherapy efficacy. A great deal of effort from academia and industry has led to the development of agents mimicking HS, and/or inhibiting HSPG modifying enzymes. Inhibitors of Sulf-2, an endosulfatase that edits the HS sulfation pattern, and inhibitors of heparanase, the endoglycosidase that produces functional HS fragments, appear particularly promising. In fact, a Sulf-2 inhibitor (OKN-007), and two heparanase inhibitors/HS mimics (roneparstat, PG545) are currently under early clinical investigation. In this review, we summarized preclinical studies in experimental tumor models of the main chemical classes of Sulf-2 and heparanase inhibitors. We described examples of different mechanisms through which heparanase and HSPGs, often in cooperation, may impact tumor sensitivity to various antitumor agents. Finally, we reported a few preclinical studies showing increased antitumor efficacy obtained with the use of candidate clinical HS mimics in combination regimens.

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http://dx.doi.org/10.2174/0929867324666170216114248DOI Listing
September 2017
17 Reads
3.853 Impact Factor

Top co-authors

Giuliana Cassinelli
Giuliana Cassinelli

Molecular Pharmacology Unit

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Nadia Zaffaroni
Nadia Zaffaroni

Molecular Pharmacology Unit

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Giovanni Luca Beretta
Giovanni Luca Beretta

Department of Experimental Oncology and Laboratories

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Enrica Favini
Enrica Favini

Molecular Pharmacology Unit

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Monica Tortoreto
Monica Tortoreto

Molecular Pharmacology Unit

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