Scientists have uncovered a mechanism that helps cancer cells survive radiation, pointing to a potential new way to make treatment more effective. The study revealed that a protein long associated with cell growth also plays a critical role in repairing DNA damage caused by radiotherapy.
The researchers found that when insulin-like growth factor 1 receptor (IGF-1R) is lost or blocked, cancer cells become less able to repair the most significant form of DNA damage: double-strand breaks. IGF-1R appears to help recruit a key repair protein to the site of damage on chromatin, the tightly packed structure that organises DNA in cells. Without this recruitment, the repair process – known as end-joining – becomes defective, leaving cells vulnerable and easier to destroy.
In the longer term, the study could help inform new treatment strategies that combine radiotherapy with drugs designed to weaken a tumour’s ability to repair DNA. The findings of the research, which was led by scientists at The Institute of Cancer Research, London, and the University of Oxford, were published in the journal Molecular Oncology. Funding was provided by Cancer Research UK, the Medical Research Council and Prostate Cancer UK.
From growth signal to DNA repair partner
Radiotherapy works by damaging the DNA inside cancer cells, creating breaks that, if left unrepaired, ultimately lead to cell death. However, many cancers develop ways to fix this damage, allowing them to survive and continue growing. Understanding these repair systems is crucial for improving treatment outcomes. The new findings suggest that one such system depends on IGF-1R.
IGF-1R is a receptor found on the surface of many cells. It is activated by growth factors and helps regulate processes such as cell division and survival. In cancer, this signalling pathway is often overactive, promoting tumour progression. Because of this, IGF-1R has already been studied as a drug target, albeit with mixed results.
The new research adds an important layer to this picture. Rather than simply helping cancer cells grow, IGF-1R appears to be directly involved in how they respond to damage. Specifically, it influences whether DNA-dependent protein kinase catalytic subunit (DNA-PKcs) can access chromatin and carry out the repairs needed to maintain the cell’s integrity.
DNA-PKcs is essential for non-homologous end joining, one of the main mechanisms that cells use to repair double-strand breaks. If this process is disrupted, DNA damage accumulates, increasing the likelihood that the cell will die – precisely the outcome clinicians hope to achieve when delivering radiotherapy.
By showing that IGF-1R loss interferes with DNA-PKcs recruitment, the study highlights a previously unknown connection between growth signalling and DNA repair machinery.
Implications for future cancer therapies
In the short term, the findings are expected to guide further research. Scientists now have a clearer lead to explore when investigating why certain cancers resist radiotherapy. The work also raises the possibility that drugs targeting IGF-1R could be repurposed or refined to enhance the effectiveness of radiation treatment.
The ultimate aim is to use the new information to create more effective combination treatments. By both damaging the cancer cells and attacking their repair mechanisms, such approaches could improve outcomes for patients whose cancers are currently difficult to treat.
There is particular interest in how this might apply to prostate cancer, where radiotherapy is commonly used. A subset of patients may benefit from therapies that exploit this newly recognised vulnerability, although further research will be needed to accurately identify those patients.
Before any clinical impact can be realised, scientists must validate the findings in more complex models that better mimic real tumours. They will also need to identify which cancer types rely most heavily on IGF-1R for DNA repair. Should these steps prove successful, the next phase would involve carefully designed clinical trials to test combination treatments in selected patient groups.
Although it is too early to estimate how many patients could ultimately benefit, the potential reach could extend beyond a single cancer type. Tumours that develop resistance to other DNA repair–targeting drugs might also be susceptible to strategies that interfere with IGF-1R.
A step towards overcoming treatment resistance
Treatment resistance remains one of the biggest challenges in oncology. Even when therapies initially succeed, many cancers find ways to adapt and survive. By uncovering a new piece of this puzzle, the current study offers a fresh direction for tackling the problem.
Corresponding author Professor Wojciech Niedzwiedz, Group Leader of the Cancer and Genome Instability Group at The Institute of Cancer Research (ICR), said:
“This discovery changes how we think about IGF-1R. Previously, it was primarily viewed as a driver of cancer growth. While that role remains important, our work suggests that it also acts as part of a cellular defence mechanism against treatment.
“What began as an investigation into a well-known growth receptor ended up revealing a critical link between signalling and cancer cell survival under treatment stress.”
First author Dr Matthew Ellis, who was working in Professor Niedzwiedz’s lab at the time of the study and is now a Research Associate in the Balmus Laboratory at the University of Cambridge, said:
“We knew that IGF-1R was linked to cancer cell survival and resistance to treatment, but it was striking to see how clearly it affected the cell’s ability to endure radiation-induced DNA damage. The effect of IGF-1R loss on DNA repair was very pronounced.
“As research continues, our hope is that insights like these will translate into more precise and effective treatments. By targeting the hidden support systems that cancer cells rely on, we may be able to tip the balance in favour of therapies like radiotherapy – making these tools even more powerful in the fight against cancer.”
The study is dedicated to the memory of Dr Valentine Macaulay, whose career – which included time at the ICR – focused on benefitting prostate cancer patients through her pioneering work on IGF-1R. Without her vision and enthusiasm for this project, it would not have been possible.
Image credit: Sangharsh Lohakare on Unsplash (modified)