Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Διαμάντω Ψυρρή, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Περικλής Φούκας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ντέιβιντ Ριμμ, Καθηγητής, Ιατρική Σχολή, Γέιλ
Ιωάννης Γ. Παναγιωτίδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ελένη Γκόγκα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Φλώρα Ζαγουρή, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Χρήστος Παπαδημητρίου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Cancer biomarkers for immune and targeted therapy
Translated title:
Cancer biomarkers for immune and targeted therapy
Summary:
PURPOSE
Analyzing biomarkers in cancer offers insights that go beyond traditional clinical factors, helping to identify patients who are likely to have a more favorable balance of benefits and risks with specific treatments. This biomarker study centers on two types of epithelial cancers: Head and Neck Squamous Cell Carcinoma (HNSCC) and Breast Cancer (BC)..
PATIENTS AND METHODS
Samples from forty-one HNSCC patients that were randomized to Cisplatin plus Olaparib (Arm A), Olaparib alone (Arm B), no treatment (Arm C) or Durvalumab plus Olaparib (Arm D) were used to evaluate for pre-specified biomarkers.
Cell lines and tissue microarrays (TMAs) were used to examine the dynamic range of HER2 biomarker and develop an assay specific to low HER2 expression and then to determine the prevalence of low-level expression in each specimen from a serial, retrospective collection of breast cancer cases.
RESULTS
A reduction in Ki67 by at least 25% was detected in 44.8% of patients receiving treatment, as determined through quantitative immunofluorescence (QIF). Post-treatment, PD-L1 levels (measured by Combined Positive Score) were notably elevated in groups (A) and (D). There was a significant increase in the expression of CD163 and Colony Stimulating Factor 1 Receptor (CSF1R) genes—markers associated with M2 macrophages—while the expression of CD80, an M1 macrophage marker, decreased.
Through calculations of detection limits, quantification, and assay linearity, we established that the expression range of HER2 in non-amplified cell lines lies between 2 and 20 attomol/mm².
CONCLUSION
Treatment with olaparib influences the tumor microenvironment by increasing PD-L1 levels and promoting pro-tumor characteristics in macrophages.
When this assay was applied to a sequential cohort of 364 breast cancer cases from Yale, results showed that 67% of the cases had HER2 expression above the quantification limit but below the levels typical of HER2-amplified breast cancer.
Main subject category:
Health Sciences
Keywords:
Translational biomarkers, Breast cancer, Head and neck cancer, HER2 assessement, PARP inhibition
Number of references:
231
File:
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Moutafi_Myrto_PhD.pdf
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