Researcher of the Month

May 2023

K. Albin Johansson Cancer Researcher (1/2022-12/2023) Heikki Kuusanmäki has a bachelor's degree in genetics and a master's degree in translational medicine from the University of Helsinki. His studies consisted of medical sciences, practical training in research groups and clinical rotations with specialist physicians. Heikki became interested in cancer and especially personalized medicine during his master’s studies. According to him, it was an exciting time, marked by the emergence of novel cancer drugs capable of selectively inhibiting mutated proteins specific to individual cancer patients. Motivated by these findings, Heikki enrolled in a PhD program, where he conducted research in the precision medicine grand challenge program, with a focus on leukemia. Heikki obtained his PhD in 2018 from the University of Helsinki with a title Targeting key survival signaling pathways for the treatment of leukemia.

Developing a novel drug testing platform

As a part of PhD studies, Heikki developed a novel drug testing platform. The platform involves placing patients-derived leukemia cells on plastic plates together with a diverse range of cancer drugs. With this method, the effectiveness of each drug in eliminating leukemia cells can be accurately evaluated. A notable improvement over previous approaches was that the platform developed by Heikki and his colleagues utilizes flow cytometry which enables assessing drug efficacy especially in the cancer cells, rather than relying on evaluations obtained from the entire patient specimen.

From a lunch conversation to a clinical trial

At the same time, in 2017-2019, a novel drug venetoclax showed promising outcomes in clinical trials for the treatment of acute myeloid leukemia (AML), an aggressive blood cancer with a poor 5-year overall survival. However, approximately half of the patients did not benefit from venetoclax. During a lunch conversation with hematologist Mika Kontro, an idea of utilizing ex vivo drug sensitivity testing to identify patients who benefit from venetoclax, was born. Excited by this thought, Heikki and Mika designed a clinical trial on venetoclax treatment in AML in collaboration with the Finnish leukemia group. Thanks to this trial, Finnish AML patients gained access to novel venetoclax treatment that was not approved in Finland during that time. The trial ended in 2022 and Heikki and Mika are now publishing the final results of the study.

Studying targeted therapies in Finland and abroad

Heikki’s main interest is still to be on the front-line development of targeted therapies and to further their application into clinical practice. He believes that close collaboration between researchers, clinicians and drug companies lead to most impactful findings in this area. Indeed, from the beginning of 2019, Heikki has worked as a postdoctoral researcher in Mika Kontro’s research group (Kontro Lab) at the Institute for Molecular Medicine Finland (FIMM), where he is responsible for the laboratory studies. Heikki also has international mobility since he has worked part-time in the University of Copenhagen during his post-doctoral studies focusing on the same topic.

New insights into venetoclax treatment

The Kontro Lab focuses on AML and especially venetoclax treatment. In Finland, approximately 220 patients are annually diagnosed with AML. In AML, the survival of leukemia cells is dependent from the BCL-2 protein. Venetoclax inhibits the antiapoptotic activity of BCL-2, making the cells more susceptible to programmed cell death.  While the introduction of venetoclax has improved the outcomes of AML patients, the majority of the responding patients relapse within 1-3 years after treatment initiation. Thus, Heikki and his colleagues are currently conducting an extensive molecular profiling on a cohort of over 100 patient samples collected during the venetoclax clinical trial. By analysing the genetic and proteomic characteristics of these samples, the group aims to gain insights in the molecular mechanisms that lead to venetoclax resistance. Another aim is to find out, whether the resistance can be overcome with novel drug combinations. 

Novel treatments against erythroid and megakaryoblastic leukemias

In a recent publication, titled Erythroid/megakaryocytic differentiation confers BCL-XL dependency and venetoclax resistance in acute myeloid leukemia, Heikki and his colleagues identified that venetoclax does not appear to be effective against erythroid and megakaryoblastic leukemias, two rare subtypes of AML. In these leukemia types, malignant cells resemble blood stem cells that produce red blood cells or platelets. Currently, few treatment options are available to these patients. However, among the more than 500 agents analysed, BCL-XL protein inhibitors were effective in killing cancer cells isolated from erythroid and megakaryoblastic leukemias. The BCL-XL protein has a similar function of preventing cells from being driven to programmed cell death as BCL-2, the target of venetoclax. At the moment, BCL-XL inhibitors are not used to treat patients, but their efficacy and safety are currently being investigated in clinical trials. The results of Heikki’s and his colleagues study show that patients with these AML subtypes would be a promising group for investigating the efficacy of BCL-XL inhibitors in clinical use.

Cycling trips, open water swimming and reading

Outside of work, Heikki draws energy particularly from different sports. Cycling trips with friends across Finland and open water swimming are his favorite activities. Additionally, Heikki likes to read science fiction and biographies, allowing him to relax and distance himself from work-related thoughts.