State-of-the-Art Tech Uncovers Potential Cancer Drug Targets

In a new study based on mouse cells internationally leading protein researchers have identified several new potential targets using state-of-the-art technology, many of which could be employed for future treatment of different types of cancers and diseases.

Protein researchers from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen have used mass spectrometry based proteomics to uncover a number of proteins which could play a critical role propagating signals within cells that can lead to uncontrolled cell growth - one of the hallmarks of cancer.

The study, which has been published in the internationally acclaimed scientific journal Cell Reports, was conducted using mouse fibroblast cells.

The researchers behind the study believe the results may prove important to the development of new so-called tyrosine phosphatase-inhibiting drugs for patients suffering from different types cancer – for example Leukaemia - as well as other types of diseases such as Noonan syndrome.

Globally, cancer is one of the leading causes of death according to the World Health Organization. In Denmark one in every three Danes develops cancer at some point in their lives, according to statistics from the Danish Cancer Society.

Advanced Cell Communication Can Inhibit Cancer Development

The researchers focused on the protein communication and signalling that takes place inside the cells. Misregulation of protein signalling often leads to an increase in the production of tumours. By understanding the mechanisms and regulation of these signals, the researchers can specifically target the proteins responsible with drugs.

Using mass spectrometry proteomics to analyse the proteins of cells treated with various growth hormones in combination with advanced data analysis, the researchers discovered proteins that manipulate the communication processes inside the cells initiated by cell receptors and thus inhibit the development of cancer.

When inhibited the prominent protein tyrosine phosphatase called Shp-2 caught the researchers’ attention.

‘This in fact leads to the deactivation of a very prominent cell growth pathway, which is the main pathway that people often try to target in cancer cells’, Professor Jesper Velgaard Olsen from the research group explains.

100 potential targets

At the beginning of the study, the researchers knew of a handful of proteins which were regulated by Shp-2. However, using the mass spectrometry analyses the researchers discovered around 100 potential new targets, revealing a far more complexity than previously considered.

Now the researchers need to do further studies to determine the role and mechanisms of these proteins. They are already following up on their first results with human cells.

‘Now we are doing follow-up projects, looking specifically at leukaemia, where the cancer cells have mutations in these different receptors which can be regulated by Shp-2’, says Postdoc Tanveer Singh Batth.

Cancer patients are often treated with tyrosine kinase inhibitors, which block pathways inside the cells to inhibit tumour growth. However, many develop resistance to current clinical inhibitors thus there is a substantial need for finding new proteins that can be used as drug targets.

Personalised Medicine

The researchers’ new discoveries can be used in the development of personalised medicine, where preventive treatments can be targeted at the patients’ personal DNA or protein expression profiles.

‘It will be a drug that can be used only in a world with personalised medicine, where it will not be given to for example all leukaemia patients, but only to those with mutations in one of the receptor tyrosine kinases where we now know this Shp-2 protein operates’, says Professor Jesper Velgaard Olsen.

Personalised medicine is gaining ground in Denmark. In 2016 the Government and the Danish Regions launched a strategy for efforts involving personalised medicine. A main part of the strategy is the establishment of a National Genome Center.

This article has been republished from materials provided by the University of Copenhagen Faculty of Health and Medical Sciences. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference
Tanveer S. Batth, Moreno Papetti, Anamarija Pfeiffer, Maxim A.X. Tollenaere, Chiara Francavilla, Jesper V. Olsen. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling. Cell Reports, 2018; 22 (10): 2784 DOI: 10.1016/j.celrep.2018.02.038.