New Gene Mutations in Cancer Could Respond to Existing Treatments

Study determines which genetic mutations in cancer will be most likely to respond to chemotherapy.

Recently, scientists at the University of Virginia School of Medicine identified 2 new cancer-causing gene mutations that may be particularly susceptible to cancer-fighting drugs already approved by FDA.

The findings could lead to more targeted therapies for different cancer types, such as lung and prostate cancer. Additional findings point to the gene mutations as the cause of early onset menopause.

The discovery suggests that cancers with mutations in the MCM8 and MCM9 genes will be most likely to respond extremely well to the same chemotherapy regimens used to fight breast cancers with the BRCA1 and BRCA2 gene mutations.

“One of the biggest problems in cancer is that we hit everything with the same hammer, and consequently some cancers are responsive and others are not. Imagine if you could find the perfect hammer for the nail — the famous personalized therapy,” said lead researcher Anindya Dutta, MD, PhD, of the UVA Cancer Center. “If a patient has BRCA1 and BRCA2 mutations, then the perfect hammer is cisplatin and olaparib. Similarly, [for other cancers,] if you could break them up into those with mutations in MCM8 and MCM9, and then hit them hard with olaparib and cisplatin, we predict that there will be much better responsiveness.”

Dutta’s new research shows that the MCM8 and MCM9 genes produce proteins that play a critical role in homologous recombination, a method cells use to repair double-strand breaks in our DNA.

These breaks are quite common, occurring thousands of times in each cell’s life. However, proteins crucial to the repair of these genes appear to be missing in cancer with MCM8 or MCM9 mutations.

That defect could make the cancer cells particularly susceptible to treatment with cisplatin and other drugs already developed to battle BRCA1 and BRCA2 mutations.

Currently there does not exist a diagnostic test for MCM8 and MCM9 mutations, but they could be revealed through whole-genome sequencing.

Dutta suggests, however, that a new, simpler test could be designed, in addition to a clinical trial to determine the effectiveness of cisplatin and olaparib in battling cancers with these mutations.

The research also revealed a correlation of genetic inactivation of the MCM8 gene and the early onset of menopause also known as premature ovarian failure. That will give scientists a new avenue to explore as they seek to better understand the condition.