Susanne Hultsch's dissertation provides new insights into the complex mechanisms of drug resistance

Susanne Hultsch’s thesis entitled " Seven shades of tamoxifen resistance - Molecular mechanisms of drug resistance in breast cancer” focuses on the cellular events that precede the development of resistance to one the most important breast cancer treatments, tamoxifen. Her doctoral dissertation was publicly examined on 23 October, with the permission of the Faculty of Medicine of the University of Helsinki.

M.Sc. Susanne Hultsch graduated from the University of Eastern Finland, in 2013 having Molecular medicine and biotechnology as her major subjects. She joined Professor Olli Kallioniemi’s research group at FIMM already in 2010, first as a summer student and later as a Master’s student. Her Master’s thesis work, supervised by Sara Kangaspeska, soon turned into a PhD project. The thesis work has been co-supervised by Olli Kallioniemi and Vilja Pietiäinen.

The overall goal of Susanne’s thesis was to create and utilize breast cancer cell line models to explore the resistance mechanisms of breast cancer and find potential prognostic markers as well as drug vulnerabilities.

Even after 70 years of research, drug resistance is still a problem and we need to learn more about mechanisms of it and vulnerabilities associated with these mechanisms to be able to treat drug-resistant cancers.

- Susanne Hultsch

Susanne’s thesis project is part of FIMM’s “Individualised systems medicine in cancer” Grand Challenge programme. Since it is almost impossible to get access to tamoxifen-resistant patient cells, commercial cell lines were used in Susanne’s thesis work. Of these, the research group generated seven tamoxifen-resistant breast cancer cell lines. Tamoxifen increases the survival of breast cancer patients but resistance to it develops frequently.

Susanne’s PhD thesis consists of three scientific publications, two of which report the characterization of the tamoxifen resistant cell lines by exome sequencing and RNA sequencing to identify possible mutations or fusion genes involved in drug resistance. Furthermore, in the first study, the role and prevalence of fusion genes in breast cancer was investigated.

In the last subproject of the thesis, Susanne focused on transcriptomic changes. RNA-sequencing data exposed gene expression and pathway changes. The identified pathways were associated with cell cycle, protein modification, and metabolism, especially with the cholesterol pathway.

Susanne has used a wide variety of wet-lab and bioinformatics methods in her thesis. Genomic analyses were combined with extensive molecular profiling, including drug sensitivity and resistance testing, high-content imaging and lysosome membrane permeability testing.

The intensive molecular profiling revealed that each tamoxifen-resistant cell line developed its own resistance mechanism and acquired individual drug vulnerabilities. Seeing the diversity of these mechanisms in only seven resistant cell lines enormously highlights the need of personalized diagnosis and therapies in treatment of tamoxifen-resistant breast cancer.

FIMM has greatly benefited from Susanne’s social, proactive and creative personality. During her doctoral student times she has been a member of several FIMM retreat committees, the FIMM PhD Student and postdoc council and the Science Basement. In addition, she has found a way to express her profound interest in science outreach by planning and organizing two very successful Science goes Art exhibitions. The pieces of science art that were created for these exhibitions can nowadays be admired at the lobbies of FIMM.

Susanne tells that she greatly values the experience and confidence she has gained during her PhD training. Her future plans are not yet settled and she is hoping to find a position where she could utilize both her scientific knowledge and creativity, be that in academia or industry.

M.Sc. Susanne Hultsch defended her doctoral dissertation entitled "Seven shades of tamoxifen resistance - Molecular mechanisms of drug resistance in breast cancer" at the Faculty of Medicine, University of Helsinki, on 23 October 2018. Professor Leonie Young, Royal College of Surgeons, Dublin, Ireland served as the opponent and professor Elina Ikonen as the custos. 

The dissertation is also available in electronic form through the E-thesis service.