Illustration of dna.

What if your cancer treatment stops working?

Photo of Emmi Kuokkanen.
Emmi Kuokkanen

Imagine the devastating situation; you have just found out that you, or a loved one have been diagnosed with cancer. Luckily, it turns out that a new promising treatment option has just become available which could also help in your situation. The treatment starts and in the follow-up appointments it seems that the treatment has started working, the tumor shrinks, and the future looks promising. Then suddenly the doctor must break the bad news, the treatment has stopped working and the tumor has started to grow, this time more aggressive than before. What happens next?

New options for cancer treatment arise on a yearly basis, but still cancers find their way to evade these drugs and continue their growth. This situation, where the cancer stops responding to a treatment and continues its growth, is called resistance. As there are various types and causes of cancers there are also various treatments, and accordingly various mechanisms how resistance is acquired. On the contrary, a fraction of cancers are caused by similar defects, and a similar treatment and resistance mechanism is common to many tumors. One example is cancers which have vulnerabilities in DNA repair – the focus area of my research.

Currently my research focuses on a fraction of this issue, breast- and ovarian cancers. Recently a new promising treatment class, PARP inhibitors, was approved for use in cancers with mutations in BRCA1, BRCA2 or other genes involved in DNA repair. The drug brought great promise to patients, but – as you might guess – resistance to treatment in patients has become an unresolved issue. As the resistance forms, the tumors often become resistant to other types of treatments too. By understanding the mechanism of how the cancers become resistant, we can better develop drugs that the cancers are unable to escape.

What I am doing in practice, is establishing cell models that would mimic the patients tumor; forming resistance upon treatment with the anti-cancer agents. The cell lines used are derived from patients, and they are treated with increasing amounts of the agents over an extended period of time. During this time, we expect cells will undergo similar changes as seen in the patients, and by monitoring these changes over time we hope to identify new mechanisms and processes of how the cancer cells behave upon resistance. Identification of this behavior may help us to develop new drugs for those patients that do not currently have any other treatment options.

The above-described research is only a small, simplified description of my thesis work and a tiny fraction of the area of research there is around cancer. There are new discoveries in the field every day, and these new discoveries again lead to new areas to discover. The field can be seen as a race, once something new and promising is discovered (and even developed to a drug), cancer often finds a way to fight back, and again new research is needed to find a workaround. Even if most cancers these days have a treatment option, there are still many patients dying of cancer every year – and as long as there are – new research in cancer is needed.

Emmi Kuokkanen
The writer is an Industrial PhD Researcher at University of Turku (Institute of Biomedicine), in collaboration with Orion Pharma (Cancer Genomics).

My current research focuses on cancers with genomic instability and defects in DNA repair. Through in vitro studies, I investigate cancers that have developed acquired resistance to therapeutic treatments, aiming to identify targets and pathways associated with this resistance. Furthermore, I am exploring cancers with chromosomal instability, working towards the development and characterization of new isogenic models to identify novel pathways and targets associated with the condition. The goal of my research is to establish and characterize in vitro cell models mimicking therapy resistance and genomic instability in cancer patients, which can be used to identify innovative approaches for tackling therapy resistance and develop novel therapies.

My thesis work is funded by Orion Corporation.