Tea Pemovska's doctoral thesis demonstrates how cancer care becomes truly personalised

Our understanding of disease mechanisms and cancer care has led to great progress in treatment and prevention during the last 50+ years. Although these leaps and bounds have improved the standard of care, clinical treatment of cancer patients is still challenged by the great molecular variability between patients with seemingly similar cancers. Thus, deep molecular profiling of patient cancer cells can be very useful when best treatment strategies are planned.

Most current efforts in cancer precision medicine focus on genomic profiling. In the thesis of M.Sc. Tea Pemovska, a complementary and perhaps more straightforward strategy was utilized. The main aim of her thesis was to develop a method for drug sensitivity testing that could be used to functionally profile leukaemia patients’ cells in order to identify personalised therapy options.

Tea has done her thesis work at FIMM in the group of FIMM-EMBL Group Leader Krister Wennerberg.  She will defend her doctoral dissertation in the Faculty of Medicine, University of Helsinki. The thesis is entitled “Individualized chemical systems medicine of acute and chronic myeloid leukemia” and in addition to Krister Wennerberg it was also supervised by Prof. Kimmo Porkka (Helsinki University Hospital Comprehensive Cancer Center).

– We focused on patients with haematological cancers, such as acute and chronic myeloid leukaemia, for both clinical and practical reasons. There is a great need of novel treatment options since the standard therapy for the acute form hasn’t changed in over 30 years and the prognosis for these patients remains poor, Tea explains.

In her thesis work, a comprehensive high-throughput drug sensitivity and resistance testing method for leukaemia patient samples was developed. The results from this functional drug sensitivity testing were further combined with deep molecular profiling and explored in a translational setting together with a team of haematologists led by Prof. Porkka.

The thesis consists of three publications, published in exceptionally high-profile journals including Nature and Cancer Discovery. The publications describe the drug sensitivity testing method as well as the “Individualized Systems Medicine” approach developed by the Personalised Medicine Grand Challenge team at FIMM in collaboration with the haematologists of the Comprehensive Cancer Center. Furthermore, the publications contain several examples of patient cases where meaningful responses were achieved and thereby how potential new clinical uses of existing cancer drugs were identified.  A highlight of the studies was the discovery that axitinib, a drug previously approved for the treatment of renal cell carcinoma, can be used to target a highly drug resistant form of leukaemia.

– Our results demonstrate that unbiased drug sensitivity profiling is a powerful way to detect unforeseen drug-disease links with clinical implications. Implementation of the data we produced led to meaningful responses in approximately 40% of patients. I feel very privileged to have been able to see the results of my work be instantly implemented and benefitting individual patients.

– Most importantly, our group was able to develop a concept that has the potential to be implemented in routine clinical care of cancer patients in the future.

From Macedonia to the Netherlands, from Finland to Austria

Originally from Macedonia, Tea graduated from Utrecht University’s Drug Innovation program in 2010 and joined FIMM the following year. She had always been interested in cancer research and when the Personalised Medicine Grand Challenge team opened a call for PhD students she thought that the project was a great match, applied and was selected together with two other students.

–I have truly enjoyed doing my thesis work at FIMM. The stimulating and international atmosphere of the institute has ensured that I have never felt like an outsider.

Tea will continue her European tour by moving to Austria. She will start as a Postdoctoral Researcher at CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, in the group of Giulio Superti-Furga, in February.

The public examination of M.Sc. Tea Pemovska's doctoral dissertation, “Individualized chemical systems medicine of acute and chronic myeloid leukemia" will take place on 20 October at 12 o’clock noon in the Lecture Hall 2, Haartman Institute (Haartmaninkatu 3). Associate Professor Neil P. Shah (Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco) is the opponent and Professor Kimmo Porkka the Custos. 

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