Thesis defence in the University of Oulu

Doctoral Candidate

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

18.10.2019 12:00

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

Opponent

Professor Jorma Isola, University of Tampere

Custos

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.

 

Dissertation

Last updated: 10.10.2019