Brazilian scientists are making progress with solving a problem that has long frustrated oncologists: after cancerous tumours in patients are subjected to radiotherapy, not all the mutated cells die. In fact some surviving cells exhibit accelerated growth despite the absence of visible irritation, so negating the beneficial effects of radiotherapy.
Now, a group of immunologists at the University of São Paulo (USP) that has been studying tumours for almost a decade, has come up with a scientific explanation for this process. This makes discovery of a pharmaceutical coadjuvant for use alongside radiotherapy to prevent tumour cell repopulations, much more viable.
The starting point was to understand was that the body’s evolutionary response to any aggressive cell damage – whether through an accident or radiotherapy – is to trigger cell repair processes to make good the damaged area. Tumorous cells repeat this behaviour. The key advance was to reveal the role of platelet-activating factor (PAF) receptors in tumour repopulation.
Using the TC-1 tumour cell line, the USP scientists subjected infected cells to assay tests that allowed the detection and collection of PAF receptor agonists generated by irradiation. Pre-treatment of TC-1 cells with the PAF receptor antagonist CV3988 before irradiation, significantly increased further cell death, supporting the protective effect of PAF on irradiated cells.
The research, published in Nature.com’s Oncogenesis earlier this year (click here to see open access details), was coordinated by prof. Sonia Jancar, of USP’s Institute of Biomedical Sciences (ICB-USP). The group, which also comprises Roger Chammas of the USP Faculty of Medicine, Ana Paula Lepique of ICB-USP and her doctoral student Ildefonso Alves da Silva Junior at the Institute of Biomedical Sciences, who is first-named author of the study.
“Silva Junior has demonstrated that radiotherapy can stimulate the production of PAF-like molecules, which in turn activate PAF receptors in tumour cells and therefore lead to increased activity by this receptor and therefore a proliferation of tumour cells,” said Sonia Jancar. She added that the study also confirmed that when macrophages in the tumour are treated with PAF receptor blockers, they become more effective.
By blocking PAF receptor signalling in sample cells from lab mice, the researchers were able to show the effect of gamma radiation on the proliferation of PAF receptor-expressing tumour cells.
The Brazilian group’s PAF receptor findings could be significant for research into leukemia, colorectal carcinoma, oesophageal cancer and breast carcinoma. Moreover, PAF is thought to have an important role in tumour growth.
According to the authors: “Association of radiotherapy with the PAF receptor antagonist represents a promising strategy for improving the efficacy of radiotherapy.”