Once known as the leading cause of cancer deaths for women in the United States, cervical cancer has been on the decline due to advances in detection technology and medical treatments over the last four decades. The latest example of this trend is a recent study by investigators with The Cancer Genome Atlas (TCGA) Research Network, which has identified novel genomic and molecular characteristics of cervical cancer that may aid in the creation of more targeted, effective drug therapies.
Through an analysis of the genomes of 178 primary cervical cancers, TCGA researchers found that more than 70 percent of cervical tumors had genomic alterations in one or both of two important cell signaling pathway. Further, researchers identified a unique set of eight cervical cancer tumors that demonstrated molecular similarities with endometrial cancers and had high frequencies of mutations in the KRAS, ARID1A and PTEN genes. Researchers unexpectedly discovered that all the tumors with genomic alterations and most of the endometrial-like tumors did not show evidence of human papillomavirus (HPV) infection, the leading cause of nearly all cervical cancer incidents.
The discovery of HPV-negative tumors with endometrial characteristics is significant in the pursuit of effective cervical cancer treatments. While current preventive vaccines are effective against the most oncogenic forms of HPV, most women who will develop cervical cancer are older than the recommended age for vaccination and will not be protected. The TCGA findings confirm that a notable portion of cervical cancers are formed from other factors not related to HPV. This signals the need for new cervical cancer treatments that specifically target genomic alterations and are effective for women regardless of age.
TCGA researchers have already begun looking at the potential applications of the research for cervical cancer treatment. During the same study, researchers examined the tumors with genomic alterations to discover whether any alterations were particularly amplified. Amplification can predict genetic responsiveness to immunotherapy, a treatment which is becoming an increasingly important component of general cancer treatments. Ultimately, several of the alterations were amplified enough to be considered effective potential immunotherapy agents, including some alterations involving the gene BCAR4, which has been shown to respond to certain breast cancer immunotherapies.