The link between human papillomavirus (HPV) and cervical cancer is well established, which is why vaccines that prevent the virus were heralded as breakthroughs when they hit the market several years ago. But some cervical tumors aren’t caused by HPV, and a half-million cases of cervical cancer are still diagnosed around the world each year, making the search for effective, well-targeted therapies a priority in the oncology community.
New research out of the National Institutes of Health’s Cancer Genome Atlas (TCGA) Research Network has uncovered a subset of eight cervical cancers—and found genetic characteristics of them that could lead to the development of personalized therapies.
The eight tumor types are mostly HPV-negative, according to a press release from the NIH’s National Cancer Institute, which co-manages the genome atlas project. The scientists also discovered a high rate of mutations in the genes KRAS, ARID1A and PTEN, making the cervical tumors similar to endometrial cancer.
“The identification of HPV-negative endometrial-like tumors confirms that not all cervical cancers are related to HPV infection and that a small percentage of cervical tumors may be due to strictly genetic or other factors," said Jean-Claude Zenklusen in the release. The research was published in the journal Nature.
In addition to looking for tumor mutations, the researchers scrutinized genes that are known to boost responsiveness to immunotherapy drugs, such as PD-1 checkpoint inhibitors. They found several such genes in cervical cancer.
They also discovered new mutated genes, as well as an abnormality in the gene BCAR4 that’s known to boost responsiveness to Tykerb (lapatinib), a chemotherapy drug used to treat breast cancer. That finding could point to BCAR4 as a target for new therapeutic regimens, they believe.
Many research groups are looking beyond HPV for new therapeutic pathways against cervical cancer. Last summer, scientists at the University of California at Los Angeles, for example, announced the discovery of a protein, cystatin E/M, that prevents the inflammation that commonly accelerates the growth of cervical tumors.
The new discoveries about cervical cancer from the Cancer Genome Atlas open up many prospects for developing a more tailored approach to treating the disease. The research also presents new questions for Zenklusen and his team to answer, they said, including whether HPV-positive and HPV-negative tumors will respond differently to personalized treatments.