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ETD

Digital archive of theses discussed at the University of Pisa

 

Thesis etd-01312022-191842


Thesis type
Tesi di specializzazione (4 anni)
Author
COPPI, ERIKA
URN
etd-01312022-191842
Thesis title
Unmet needs in oncology: focus on drug development strategies in non-Hodgkin's lymphoma, bladder cancer, and breast cancer
Department
MEDICINA CLINICA E SPERIMENTALE
Course of study
FARMACOLOGIA E TOSSICOLOGIA CLINICA (non medici)
Supervisors
relatore Prof. Danesi, Romano
Keywords
  • oncology
  • non-Hodgkin's lymphoma
  • bladder cancer
  • breast cancer
  • chemotherapy
Graduation session start date
21/02/2022
Availability
None
Summary
The advancements in the knowledge of tumor biology over the last 10 years have revolutionized the field of cancer diagnostics and treatments. A number of novel target therapies have been registered in several onco-hematological tumors, allowing longer survival in metastatic cancer patients. Important results have been obtained in different diseases, including Hodgkin lymphoma, bladder, and breast cancer, with the registration of specific antibody-drug conjugates (ADC). In patients affected by Hodgkin lymphoma, thanks to the registration of bretuxumab vedotin, that is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), has been obtained a Complete Response Rate of 88%, Overall Response Rate of 93% and Favorable Safety Profile. Similarly, important advancements have been obtained in advanced bladder cancer, with the enfortumab vedotin, an ADC directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer: Overall survival and progression-free survival was longer in the enfortumab vedotin group of patients than in the chemotherapy group. Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).
Also in HER2-positive breast cancer have been registered important results, within the trial using the combination of tucatinib, an HER2 tyrosine kinase inhibitor, and the anti-HER2 monoclonal antibody trastuzumab, showing increased anti-tumor activity in vitro and in vivo compared to either treatments alone.
This research aims to highlight the Clinical Trials studies carried out and in progress on the above drugs, the analyses and the results that are becoming the next strategies for Hodgkin lymphoma, bladder and HER2-positive breast cancer.
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