Personalised leukaemia treatment and faster adoption of new drugs: four breakthroughs leading towards more effective cancer treatment

5.1.2018
Our understanding of the genetics of cancer is constantly increasing. At the same time, we are accumulating more information of the genetic variations which increase cancer susceptibility, allowing the development of more effective cancer treatments. These four breakthrough studies about the "fifth letter" in the human genome, adoption of new cancer drugs, personalised cancer treatment and blood cancers were achieved by the University of Helsinki’s cancer researchers during the past year.

To comprehend the biology of cancer, we must have an extensive understanding of the human genome and the genetic variations that increase susceptibility to cancer as well as the genetic mutations found in cancer tumours.

The Centre of Excellence in Tumour Genetics Research, which launched at the Faculty of Medicine at the beginning of 2018, focuses on the mutations that occur in cancerous tissue. Led by Professor Lauri Aaltonen, the research continues the work of the Finnish Centre of Excellence in Cancer Genetics Research, which closed at the end of 2017.

"Once we understand the detailed significance of the structure of the genome, we will also be able to better decipher the genetic changes we see in cancerous tumours," says Aaltonen.

1. DNA’s "fifth letter" reveals information about cancer susceptibility

Aaltonen considers the greatest recent achievement of the Centre of Excellence to be the study conducted by Professor Jussi Taipale’s group and published in Science in 2017, discussing DNA’s "fifth letter", which shapes the way the genetic code is read.

The order of the letters in the human genome – A, C, G and T – has been known since 2000. In addition to these four letters, the Cs in combinations of C and G can be transformed in the cell into a “fifth letter” of the genome.

Understanding the order of the DNA base pairs, or letters, is necessary for applying genome data in medicine. Cancer research will in the future be able to provide more information on which individuals are more susceptible to tumours on account of their genetics. This would be valuable information for cancer prevention.

"A better understanding of the biology of cancer will also open new opportunities for developing cancer treatments. That is another area where major strides are constantly being taken and applied to clinical work," says Aaltonen.

2. New opportunities for treating leukaemias

Blood cancers provide a good model for studying more effective, personalised cancer treatments. This is because, unlike with solid tumours, it is relatively easy to extract samples directly from the patient’s blood or bone marrow.

"The goal of our research is to study leukaemia patients as closely as possible to recognise the individual characteristics which will allow us to further develop personalised treatments," says Kimmo Porkka, professor of clinical haematology.

The challenge is that leukaemia causes between two and six mutations on average, but when the potential combinations of these mutations are considered, the result is thousands of different varieties of cancer.

"In practice, each patient has a slightly different form of the disease," says Porkka.

Some leukaemia patients respond well to traditional chemotherapy, but more than half see no benefit from it. However, all leukaemia patients are currently treated in the same way, as there is no existing data on who will respond to the treatment and who will not.

Each patient has a slightly different form of leukaemia, but the treatment is the same.

Studies are underway to map the genome of the patients’ leukaemia cells and germline cells and to conduct drug susceptibility testing on their cancer cells.

"We test up to 500 different medications on the cells of an individual patient, which lets us determine already at the test tube stage which drugs will be helpful."

Combining this information with the molecular mapping of the genomes of both the patient and the cancer cell may reveal biomarkers, or the characteristics in the genome which will enable medical professionals to choose a personalised treatment for each patient’s cancer.

"In 2017, we discovered several biomarkers which help us predict what kinds of treatments we should use," Porkka explains.

One significant discovery relates to BCL2 antagonists, proteins which can induce programmed cell death in the cancer cells of a patient group with a specific set of genetic characteristics. Another has to do with the cortisone medication used in autoimmune diseases, which seems to be highly effective in treating a certain type of acute leukaemia.

To support the research in blood cancers, the University last year established the professorship in translational haematology, which is held by Satu Mustjoki.

According to Mustjoki, the biggest achievement of her research group during the last year was the discovery of the genetic mutations found to underlie LGL and T cell leukaemias, increasing the understanding of the generation mechanisms of these diseases. New potential treatments have also been uncovered for these cancers, which are difficult to treat.

During the new year, Mustjoki’s group intends to learn to understand the immunological characteristics of various cancers.

"We want to find out why the immune system cannot destroy the cancer cells, and how we could make it more effective."

3. Personalised cancer drug treatment on the horizon

At the moment, the use of genetic information in selecting cancer treatments is still in the research stage, with only a few biomarkers being actively used.

"Fully personalised treatment is still a thing of the future, but not too distant a future," says Professor Porkka.

This is also the goal of 2017 Helsinki Challenge-winner iCombine, a team seeking to develop an AI solution combining nearly a decade of genetic and drug susceptibility data and providing personalised medication suggestions for cancer patients based on genetic information.

In addition to combining huge amounts of information, another hurdle on the way from the laboratory to the clinic is that even new uses for existing, tested medications require an approval process of couple of years.

However, that is a brief amount of time compared to the average development process of new drugs, which can be 15 years.

4. Clinical testing of cancer drugs to be adopted faster

Launched in 2017, the TEHO project for adaptive clinical trial design aims to promote the clinical testing of cancer drugs. The project seeks to develop an operational model that would enable trials with a significantly smaller number of patients and lower costs than is required for traditional trials.

In addition, using a model that employs molecular biology and genetics to select patients for the trial would speed up the journey of a drug candidate to clinical use and reduce the exposure of individual patients to ineffective doses in the course of trials.

The project is led by Docent Juha Klefström of the University of Helsinki. Klefström’s research project cultivates breast cancer samples and conducts drug testing on them in the laboratory. In addition to new drug candidates, new combinations of existing drugs are also tested on the samples.

For more information on this research and its achievements, read the article Killing cancer.

 

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