Genetically modified fish assisting in the fight against cancer

Prostate cancer is the most common form of cancer in men globally; and the disease appears to become even more prevalent in the coming years.

As it’s associated with the western diet, which is becoming increasingly common in developing countries as well.

“This is why being able to recog-nise aggressive forms of prostate cancer is highly valuable. There’s a lot of evidence to indicate that ordinary forms of cancer also use molecules in similar ways, so our research may also be of importance to other patient groups,” says Maréne Landström, who carried out the study together with Jonas von Hofsten at Umeå University.

The research that led to the breakthrough began in 2012, when she received a large grant. This gave her the opportunity to recruit doctoral students to investigate signalling molecules that have a part to play in inflammation and tumour progression. Pilot trials revealed that the special protein TRAF6 was important in the signalling chain resulting in prostate cancer becoming aggressive.

Professor, senior consultant (attending) physician at the Department of Medical Biosciences.

ImageMattias Pettersson

By analysing the expression and function for TRAF6 in both tissue samples from men with prostate cancer and genetically modified zebrafish — with a great deal of assistance from the genome editor CRISPR-Cas9 — researchers have been able to position TRAF6 as a new and important key protein in the signalling chain for the Wnt3 function in Wnt3a, a growth factor that promotes tumour growth and cancer spread.

“We’ve found a new piece of the puzzle that makes it possible to understand molecular mechanisms in the progression of cancer more closely. In the long run, this may make it possible to recognise aggressive tumour cells in patients at an earlier stage and help to bring about new, improved treatments. Many prostate cancer treatments nowadays result in side effects and relapse, but we hope our discovery will help to remedy this. This greater understanding will also make it possible to develop new drugs in future."

Maréne Landström and her research team are now continuing their studies into TRAF6 and its significance as regards prostate cancer. Karthik Aripaka, a member of the team, completed his doctorate in late 2019, and in 2020 the researchers are investigating the role of the lymphatic system and blood vessels in the spread of prostate cancer. The research team will be using zebrafish for their trials here as well.

“The advantage of zebrafish is that we see results within six to twelve months. With mice it takes about three years to get similar responses. The transparency of the fish makes it easy to monitor the spread of the metastases.”

Maréne Landström is also running another project testing a potential new cancer drug. Based on her previous research, this research team has found promising new biomarkers for aggressive prostate and renal cancer. TRAF6 has an important part to play here as well, but in a different part of the signalling chain.

This article was first published in the magazine Think no. 1 2020.