Master of Science Tiia Honkanen
Faculty and research unit
University of Oulu Graduate School, Faculty of Medicine, Cancer and translational medicine research unit
Field of study
Oncology and radiotherapy
Date and time of the thesis defence
Place of the thesis defence
Lecture hall 7, Oulu University Hospital
Topic of the dissertation
More efficient use of HER targeting agents in cancer therapy
Professor Jorma Isola, University of Tampere
Docent Jussi Koivunen, Oulu University Hospital
HER protein targeting agents could be utilized more efficiently in cancer therapy
This current thesis investigated possible markers, which could be used to predict HER2-positive breast cancer patients’ sensitivity to HER2-therapy and studied the role of HER2 and HER3 proteins for cancer stem-like cells in ALK translocated non-small cell lung cancer.
HER2 targeting agents have significantly improved the prognosis of HER2-positive breast cancer patients. HER2 therapy is given according to the HER2 status of the patient’s tumor, due to a lack of other predictive factors for the therapy. However, great variation is seen in the treatment outcomes among HER2-positive breast cancer patients; some patients receive excellent responses to the treatment, but still a major part of the patients is either primary refractory for the treatment or will develop a resistance against it.
Treatment resistance can be developed by various mechanisms. Cancer stem-like cells are one cause for therapy resistance and cancer recurrence. The number of these cells in tumors is quite low compared to the bulk cancer cells but they have been shown to be resistant to several cancer therapies. Cancer stem-like cell targeting agents are still, however, unavailable in the clinics.
The results of this thesis demonstrated that a high number of cytotoxic T cells, together with a high number of M1-like macrophages in the center of the tumor, are promising prognostic factors in metastatic HER2-positive breast cancer and these markers can also predict the disease progression and HER2 therapy sensitivity. The results also highlight the role of HER2 and HER3 for the cancer stem-like cells in ALK translocated non-small cell lung cancer and showed that HER2-HER3 -dependent cancer stem-like cells mediated the therapy resistance in the disease.
In conclusion, the results of this thesis suggests that patients with high center tumoral infiltration of cytotoxic T cells and M1-like macrophages could be treated in a less-intensive manner, and that targeting of HER2 and HER3 proteins could lead to more efficient elimination of cancer stem-like cells and should be further studied.
Last updated: 10.10.2019