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Betydelsen av PDGF vid Trippelnegativ Bröstcancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2022 (Swedish)Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
Abstract [en]

Triple negative breast cancers (TNBC) are defined by the absence of estrogen andprogesterone receptors and the absence of HER2 protein overexpression. TNBC cancersrepresent a heterogeneous breast cancer subtype with poor prognosis. The heterogeneity of thedisease has limited the successful development of targeted therapy in unselected patientpopulations. Currently there are no approved targeted therapies for TNBC. However, intenseresearch is ongoing to identify specific targets and develop additional and better systemictreatment options. Recently researchers have found that the PDGF pathway plays a significantpart in communication between cancer cells and cells in the surrounding tissue. In thisliterature study evaluated if the PDGFR inhibition is a treatment strategy for triple negativebreast cancer. Method: literature original articles from database Pubmed was used in thisstudy. Results: results show that PDGF is more overexpressed in tissue cells than tumor cells.PDGF isoforms like PDGFRalfa and PDGF-C can increase the risk of distant recurrence tocentral nervsystem and early recurrence of primary breast cancer. The TNBC subtype (MES)is more likely to overexpress PDGF and inhibition with PDGF specific aptamer have shownsignificantly decreased tumor cell growth. Triple combination treatment with MEK1/2 and(JAK2) inhibitors resulted in significant reduction of cell growth and immunological inducedcell death through CD8+ t-cells. Single treatment with PDGFR inhibitors like Ponatinib andSunitinib reduced cell growth and cell migration in TNBC, but a combination treatment withDoxorubicin showed far greater inhibitor effect on cell growth and migration it also causedcell death. Chemotherapy Doxorubicin combination with a PDGFR- inhibitor resulted inbetter treatment compared to a single PDGFR- inhibitor to treat TNBC.Conclusion: It has been proven that PDGF isoforms have different significance in thedevelopment of TNBC. The PDGFC ligand is significantly more expressed in TNBCcompared to other PDGF isoforms. Ligand and receptor binding PDGFC-PDGFRα expressionis increased during breast cancer progression. PDGFRbeta signaling pathway plays a crucialrole in mediating vascular properties and therefore may be a good marker for reducing newvessel formation in endothelial cells. Combination therapy appears to be promising drugtreatment in TNBC. PDGFR inhibitors combined with cytostatic drugs or JAK & MEK1/2inhibitors can provide a pharmacological synergistic effect or activate the immune systemCD8+ T cells. Combination therapy reduces emergence of resistance mechanisms, howeverthere is a lack of studies on toxicity side effects. Nyckelord: Trippelnegativ bröstcan

Place, publisher, year, edition, pages
2022. , p. 34
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-496059OAI: oai:DiVA.org:uu-496059DiVA, id: diva2:1734619
Educational program
Bachelor of Science Programme in Pharmacy
Examiners
Available from: 2023-02-08 Created: 2023-02-06 Last updated: 2023-02-08Bibliographically approved

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