Examining Genomics in the Treatment of Cervical Cancer

Researchers from Yale Cancer Center have created a platform to identify genetic mutations that might drive cervical cancer.

Could targeted therapy play a larger role in the treatment of cervical cancer in the near future? Researchers from Yale Cancer Center believe they are one step closer to finding out, according to new study findings published in the Proceedings of the National Academy of Sciences.

Targeted therapies can aim for and block the activities of certain mutations. In several cancer types, such as breast, colorectal and lung, researchers have been able to target specific mutations, which has benefited patient response. Currently, only two targeted therapies are approved by the Food and Drug Administration (FDA) to treat cervical cancer: Avastin (bevacizumab) and Keytruda (pembrolizumab).

The researchers have been studying tumor genomics in cervical cancer and built a powerful research platform, according to the study, in which researchers collected fresh-frozen tumor samples from 69 patients with cervical cancer. Next, they performed whole-exome sequencing, a process for sequencing protein-coding regions of a person’s genome. This technique helped them to identify genetic mutations that could drive cervical cancer.

At least one mutated gene in a cellular signaling pathway known as ERBB2/PI3K/AKT/mTOR was found in more than 70% of the tumors. “We have identified many driving genetic mutations in cervical cancer, and we have started preclinical validation of drug candidates that target and block the activities of these mutations,” Dr. Alessandro Santin, leader of the Disease Aligned Research Team for the Gynecologic Oncology Program at Yale Cancer Center and Smilow Cancer Hospital at Yale New Haven, said in a press release.

To see if these mutations could be targeted by medications already approved by the FDA for other types of cancer, the researchers combined two drugs, Aliqopa (copanlisib), and Nerlynx (neratinib), and tested them in cervical cancer cells and animal models. They found that the two-drug combination was effective. Aliqopa is a type of kinase inhibitor that inhibits the PI3K pathway and is currently approved to treat follicular lymphoma that has relapsed. Nerlynx is a targeted therapy used to treat HER2-positive breast cancers and blocks certain proteins that can potentially keep cancer cells from growing and may kill them. In previous studies, therapy combinations have proven to work better in patients with cancer than single medication treatment, the researchers noted.

The next step is to hopefully study this in early clinical trials. “This is only the first step,” Santin, who is senior author on the study, said. “Many other potentially ‘druggable’ mutations and deranged pathways were identified in our work that may now go through preclinical validation using agents highly specific for these targets.”