New treatment strategy could overcome drug resistance in testicular cancer

The Institute of Cancer Research (ICR)

Men with testicular cancers called testicular germ cell tumours - which are most common in younger men - could benefit from a new combination of treatments if their chemotherapy stops working.

Micrograph of seminoma testes showing lobules of uniform cells separated by delicate septae of fibrous tissue.
Micrograph of seminoma testes showing lobules of uniform cells separated by delicate septae of fibrous tissue. Source: Wikimedia Commons CC BY SA 4.0

In a new study, scientists at The Institute of Cancer Research, London, show that a targeted drug blocking the action of a cancer-driving protein can kill testicular cancer cells and, alongside chemotherapy, could reverse drug resistance.

Building on previous work at the ICR, the scientists analysed the activity of proteins called receptor tyrosine kinases, and identified activity of insulin growth factor receptor-1 (IGF1R) in testicular cancer cells.

Receptor tyrosine kinases play a critical role in important cellular processes such as cell growth and division, and are implicated in the development and progression of many types of cancer.

Increased sensitivity to platinum-based chemotherapies

In the study, published in the Journal of Pathology, the researchers discovered that IGF1R was highly active in some testicular cancer cells, compared with normal tissue.

Molecularly depleting IGF1R or silencing IGF1R activity using chemical inhibitors reduced tumour cell growth – particularly testicular germ cell tumour cells with the highest levels of IGF1R activity.

Importantly, blocking the protein’s activity in chemotherapy-resistant cells increased their sensitivity to platinum-based chemotherapy drugs – meaning that IGF1R inhibitors could prove to be a treatment for drug-resistant testicular germ cell tumours.

Some existing IGF1R inhibitors have been tested in clinical trials for other types of cancer.

The research was funded by the Bob Champion Cancer Trust, Medical Research Council and the Institute of Cancer Research, with support from the NIHR Biomedical Research Centre at the ICR and The Royal Marsden NHS Foundation Trust.

Overcoming resistance to chemotherapy

Study leader Professor Janet Shipley, Professor of Cancer Molecular Pathology at the ICR, said:

"Although rare, testicular germ cell tumours represent the leading cause of death from solid cancers in the 20–40 age group.

"Our study has identified and shown a link between high levels of insulin growth factor receptor-1 and testicular cancer cell growth, including cells resistant to platinum chemotherapy.

"Our study raises the possibility that combining drugs that inhibit insulin growth factor receptor-1 with chemotherapy could prove to be an effective treatment strategy for men with chemotherapy-resistant, testicular germ cell tumours.”

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