Drugs that are designed to block IGF-1R have been tested in early clinical trials for people with cancer. These drugs work well in some people but not for others, and it is not clear why.
To tackle this dilemma, Dr Valentine Macaulay’s team at the University of Oxford have, with funding from Breast Cancer Campaign, been searching for a protein that could act as a ’biomarker’ to find out which breast cancers IGF-1R-blockers will work for.
In a paper published in the journal Cancer Research, Dr Macaulay’s team used breast cancer cells grown in the lab, to find proteins that affect how well breast cancer cells are killed by IGF-1R blockers. They show that breast cancer cells with low amounts of the protein DVL3 respond better to treatment with IGF-1R-blockers than those with lots of DVL3. The researchers also confirmed that DVL3 could be tested for in tumour samples, and around 50% of breast and prostate cancer samples they looked at had low levels of DVL3. In patients with a range of different types of cancer who had been treated with IGF-1R blockers, they found that patients with low amounts of DVL3 in their cancers were more likely to benefit from IGF-1R blockers than patients whose cancers had a lot of DVL3.
Dr Lisa Wilde, Director of Research at Breast Cancer Campaign, said:
“This is the first step to unlocking a new type of treatment, IGF-1R blockers, for the women with breast cancer who are most likely to benefit."
"We now hope that Dr Macaulay’s findings can be confirmed and incorporated into clinical trials for IGF-1R blockers so that we can see whether this exciting new treatment can be targeted to the right people and make a real difference to breast cancer patients, bringing us one step closer to our goal that by 2025 improved and more personalised treatments will cut mortality from breast cancer by half."
In parallel with this work on breast cancer, Dr Macaulay’s team conducted experiments in prostate cancer. This part of the work was funded by the Oxford-based charity UCARE (Urology Cancer Research and Education). As with breast cancer, the results showed that reducing the amount of DVL3, or blocking DVL3 with a chemical drug, made the prostate cancer cells easier to kill with IGF-1R blockers. Dr Macaulay’s team confirmed this result using tests in mice.
Valerie Berry, Development Officer at UCARE, said:
“We are very happy to have been able to support this work, which will help cancer researchers to find out which prostate cancer patients may respond to treatment with IGF-1R blockers. This work also suggests that it may be beneficial to test combinations of drugs that block DVL3 and IGF-1R."