Study Finds Gene Linked to Treatment-Resistance in Patients with Testicular Cancer

Scientists have uncovered several new genetic mutations that could drive testicular cancer, and have identified a gene that may play a role in tumors becoming resistant to available therapies.

A new major research study, led by scientists at The Institute of Cancer Research, London, is the first to use state-of-the-art sequencing technology to explore testicular germ cell tumors in detail. Testicular germ cell tumors make up the vast majority of testicular cancers and are the most common cancers in young males.

The researchers used whole-exome sequencing, a genetic technique, to examine tumor samples from 42 patients with testicular cancer. The samples were from patients treated at the Royal Marsden NHS Foundation Trust. They found several new chromosome duplications, as well as other abnormalities that could contribute to the development of this cancer. In addition to new chromosome duplications, they confirmed a previous association with the gene KIT.

The study also found defective copies of a DNA repair gene called XRCC2 in a patient who had developed resistance to platinum-based chemotherapy. The researchers were able to verify the link between the gene and platinum resistance by sequencing an additional sample from a separate platinum-resistant tumor. Patients with testicular cancer who develop resistance to platinum-based chemotherapy generally have a poor long-term survival rate. Currently, around three percent of patients develop this resistance, and this study provides a potential reason why.

“This study has used the latest DNA sequencing technologies to provide a window into the development of testicular cancer, and reveals some potentially important clues as to how the disease could be treated more effectively,” said Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London. “Survival rates for testicular cancer are generally very good, but a subset of men don’t respond to standard platinum chemotherapy, and the new research has identified a possible genetic cause for that drug resistance. Knowing which are the key genetics driving a cancer’s development or helping it dodge the effects of chemotherapy is crucial to help us use existing drugs more effectively and to design the next generation of drugs for personalized medicine.”

The authors noted that additional studies with a larger number of patients is now needed to focus in particular on platinum-resistant tumors to lead to new treatment options for this patient population.

The study, which was funded by the Movember Foundation, was published in Nature Communications.

Source: The Institute of Cancer Research

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