Testicular Cancer Drug Resistance Linked to Specific Gene

Research identifies how tumors resist current treatments.

The discovery of genetic mutations that drive testicular cancer may also have uncovered a gene that potentially helps tumors become resistant to current treatments.

The study, published recently in Nature Communications, was the first to utilize a state-of-the-art technology called whole-exome sequencing. This technique provides a detailed evaluation of testicular germ cell tumors, which comprise the vast majority of testicular cancers.

"Our study is the largest comprehensive sequencing study of testicular tumors published to date, describing their mutational profile in greater detail than has been possible using previous technologies,” said study lead Clare Turnbull, MD, in a press release. “We have identified new potential driver mutations for this type of cancer, and provided new evidence of a link between mutations in the gene XRCC2 and platinum treatment-resistant tumors.”

The technology revealed a number of new chromosome duplications and abnormalities that may contribute to the development of testicular cancer, in addition to proving a previous link with the gene KIT.

The study also found defective copies of the DNA repair gene XRCC2 in a patient who became resistant to platinum-based chemotherapy. The researchers were able to confirm the link between XRCC2 and platinum chemotherapy resistance through the sequencing of an additional sample from another platinum-resistant tumor.

Despite the fact that testicular cancer generally responds well to treatment, resistance to platinum-based chemotherapy is linked to poor long-term survival rates. The study offers a clue as to how 3% of patients develop resistance to platinum chemotherapy, in addition to general information on testicular germ cell tumors.

"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,” Professor Paul Workman, chief executive of The Institute of Cancer Research in London, said in a press release. “Knowing which are the key genes 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."